RU2772909C2 - Carbapenem compounds - Google Patents

Abstract

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to carbapenem compounds, stereoisomers, pharmaceutically acceptable salts thereof, suitable for treating bacterial infections, in particular, medication-resistant bacterial infections, as well as pharmaceutical compositions containing such compounds and application thereof in the treatment of a bacterial infection.

EFFECT: creation of carbapenem compounds suitable for treating bacterial infections.

28 cl, 1 tbl, 601 ex

Description

FIELD OF TECHNOLOGY TO WHICH THE INVENTION RELATES

The present invention describes carbapenem compounds, their stereoisomers, pharmaceutically acceptable salts or N -oxides, which are useful in the treatment of bacterial infections, in particular drug-resistant bacterial infections. Also described in the present invention are processes for the preparation of compounds, pharmaceutical compositions of these compounds, and their use in the treatment of bacterial infection.

BACKGROUND OF THE INVENTION

Antimicrobial resistance is the most important problem in antibiotic therapy. One mechanism for the development of resistance results from the activity of enzymes that deactivate a particular class of antibiotics by hydrolysis, such as the β-lactam ring of β-lactam antibiotics. In the mid-1980s, it was discovered that the enzymes that are responsible for the deactivation of β-lactams are β-lactamases, in particular extended spectrum β-lactamase (ESBL). ESBL is produced primarily by the Enterobacteriaceae group (Chaudhary et al., Indian Journal of Medical Microbiology, 2004 , 22(2), 75-80, Extended Spectrum β-Lactamases (ESBL)-An Emerging Threat to Clinical Therapeutics).

Risk factors involved in ESBL expression are prolonged hospitalization or intensive care unit stay, increased disease severity, use of a central venous or arterial catheter or urinary catheter, assisted mechanical ventilation, hemodialysis, emergency cavitary surgery, gastrostomy or jejunostomy, colonization intestinal micro-organisms before administration of antibiotics, particularly hydroxyimino-β-lactams (Falagas et al., Journal of Antimicrobial Chemotherapy, 2007 , 60, 1124-1130, Risk factors of carbopenem-resistant Klebsiella pneumoniae infections: a matched case-control study) .

Antibiotics that are used as a last resort because of their broad spectrum of antimicrobial activity are carbapenems. Carbapenems such as imipenem (US Patent No. 4194047 A), meropenem (EP No. EP0126587 B1), ertapenem (EP No. EP0579826 B1) and doripenem (EP No. EP0528678 B1) are injectable ultra-broad spectrum antibiotics. actions. These antibiotics cause cell death by binding to penicillin-binding proteins (PBPs) and inhibiting cell wall biosynthesis. The emergence of carbapenemases belonging to class A and class D β-lactamases threaten their clinical applicability.

The presence of the hydroxyethyl side chain in carbapenems is reported to impart stability to these compounds. (Sumita, Y et al., Journal of Antibiotics, 1995 , 48(2), 188-190).

Sunagawa M et al., Journal of Antibiotics , 1997 , 50(7), 621-627, describes carbapenem compounds having antimicrobial activity.

There are no reports of carbapenem compounds with activity against gram-negative bacteria resistant to carbapenems. Therefore, the development of a new carbapenem compound with a broad antibacterial spectrum, preferably a compound with high activity against resistant bacteria that produce β-lactamase, is desirable.

There is still a huge unmet medical need for new antimicrobial agents due to the emergence of bacterial resistance to current therapies.

GOAL

The purpose of the present invention is to obtain carbapenem compounds, their stereoisomers, pharmaceutically acceptable salts or N -oxides.

Still another object of the present invention is to provide methods for the preparation of carbapenem compounds and pharmaceutical compositions containing these compounds.

A further object of the present invention is to provide a method for preventing or treating a bacterial infection and for producing carbapenem compounds as broad spectrum antibacterial agents.

SUMMARY OF THE INVENTION

The present invention relates to new carbapenems. In particular, the present invention relates to a compound of formula ((I), (Ia) or (Ib) or a stereoisomer, internal salt, N-oxide or pharmaceutically acceptable salt thereof. Compounds of formula (I), (Ia) or (Ib) or their stereoisomer, internal salt, N-oxide or pharmaceutically acceptable salt may be useful in the treatment of bacterial infections.The present invention relates to compounds of formula (I)

(I)

(I)

or their stereoisomer, internal salt, N-oxide, prodrug or pharmaceutically acceptable salt:

where:

A is -NR ⁰ R or -OR ^z ;

Z is -H or -CH ₃ ;

X is -S- or -CH ₂ -;

R ^z is isoxazolyl;

R ⁰ is hydrogen or C _1-6 alkyl which is optionally substituted with one or two substituents selected from halo, hydroxyl, cyano, carbamoyl, -SO ₂ NH ₂ and C _1-6 alkoxy;

R represents:

1) -(CH ₂ ) _n C(=O)R ² ,

2) -(CH ₂ ) _n C(=S)R ² ,

3) -(CH ₂ ) _n SO ₂ R ² ,

4) -C _1-6 alkyl optionally substituted with -C _3-6 cycloalkyl, or

5) -CH(=NH), or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S;

n is an integer selected from 0, 1, 2, 3, 4, 5 and 6;

R ¹ is:

1) -(CH ₂ ) _0-6 -AryC,

2) -(CH ₂ ) _0-6 -HetC,

3) -(CH ₂ ) _1-6 NH(C=NH)NH ₂ , or

4) C _2-6 aminoalkyl optionally substituted with a) -C(=O)C _1-6 alkoxy, b) -C(=O)-pyrrolidinyl substituted with -NR ^x R ^y ,

c) -CR ^x =NR ^x , or

d) -COO-phenyl;

^R2 is:

1) H

2) C _1-6 alkyl optionally substituted with 1, 2 or 3 substituents independently selected from halogen, -OH, -CN, C _3-8 cycloalkyl, -(CH ₂ ) _0-1 C(=O)NR ^x R ^y , -NR ^a R ^b , C _1-6 alkoxy, -OC(=O)C _1-6 alkyl, -P(=O)(C _1-6 alkoxy) ₂ , -COOH, -COOC _1-6 alkyl , -SO ₂ C _1-6 alkyl, -S(=O)C _1-6 haloalkyl, -SCHF ₂ , Het A, AryA, -S-AryA, azetidine and azetidinone optionally substituted with C _1-6 hydroxyalkyl,

3) C _3-8 cycloalkyl substituted with C _1-6 haloalkyl or -NR ^x R ^y ,

4) -(CH ₂ ) _0-3 -CR ^k =NOC _1-6 alkyl, optionally substituted-COOR ^x ,

5) -C(=O)NR ^x R ^y ,

6) -C(=O)C _1-6 alkoxy,

7) -NR ^x R ^y ,

8) -OH,

9) -COOH,

10) C _1-6 alkoxy,

11) C _1-6 haloalkyl,

12) C _1-6 haloalkoxy,

13) AryA or

14) HetA;

R^four represents-COO^-or -COOR⁵;

R ⁵ is hydrogen, a carboxylic acid protecting group, or an ester prodrug moiety;

AryA represents

1) a substituted or unsubstituted 5 or 6 membered aromatic ring with 0, 1, 2, 3 or 4 heteroaromatic ring atoms independently selected from N, O and S, or

2) a substituted or unsubstituted 9- or 10-membered bicyclic aromatic ring with 1, 2, 3, 4, 5 or 6 heteroaromatic ring atoms independently selected from N, O and S;

HetA is a substituted or unsubstituted 5-10 membered saturated ring with 1, 2, 3 or 4 heteroaromatic ring atoms independently selected from N, O and S, where any S atom in the ring is optionally oxidized;

AryC is 1) a substituted or unsubstituted 5- or 6-membered aromatic ring with 0, 1, 2, or 3 heteroaromatic ring atoms independently selected from N, O, and S, where the N atom is optionally quaternized with -CH ₃ , or

3) a substituted or unsubstituted 7-10 membered bicyclic aromatic ring with 0, 1, 2 or 3 heteroaromatic ring atoms selected from N, S, and O;

HetC is a substituted or unsubstituted 4-8 membered saturated ring with 1 or 2 heteroaromatic ring atoms selected from N, O or S;

R ^a is hydrogen, C _1-6 alkyl, C _3-8 cycloalkyl, -CR ^x (=NR ^x ), -C(=NR ^x )N(R ^x ) ₂ , -CH ₂ C(=O)N (R ^x ) ₂ , -(CH ₂ ) _1-6 OR ^x or -SO ₂ C _1-6 alkyl;

R ^b is hydrogen or C _1-3 alkyl;

^Rc represents

1) H

2) -C _1-6 alkyl, optionally substituted with -NR ^h R ^j , -CN or -OH,

3) -(CH ₂ ) _1-3 C(=O)NR ^x R ^y ,

4) -(CH ₂ ) _1-3 C (= O) NHCH ₂ CH ₂ OH,

5) -(CH ₂ ) _1-3 C(=O)NHOCH ₃ ,

6) -(CH ₂ ) _1-3 C(=O)NHOBn,

7) -C _1-6 alkoxy,

8) pyridinyl,

9) -(CH ₂ ) _1-3 -pyrrolidinyl, optionally substituted with -C(=O)NR ^x R ^y ,

10) tetrahydro-2H-pyran-4-yl,

11) -(CH ₂ ) _1-3 C (= O) - diazepanil,

12) -(CH ₂ ) _1-3 C(=O)- pyrrolidin-1-yl substituted with NR ^x R ^y ,

13) -C(=NH)- pyrrolidin-1-yl, optionally substituted with NR ^x R ^y ,

14) -(CH ₂ ) _1-3 -pyranyl optionally substituted with 1 or 2 substituents selected from oxo and methoxy,

15) -(CH ₂ ) _1-3 -pyridinyl, optionally substituted with one or more groups selected from -CH ₃ , -OH and oxo,

16) -phenyl-C(=O)- pyrrolidinyl-NR ^x R ^y _,

17) -phenyl-C(=O)-piperazinyl or

18) -phenyl- (CH ₂ ) _1-3 - NR ^x R ^y ;

R ^d is hydrogen, C _1-3 alkyl, C _1-3 hydroxyalkyl, or C _1-3 cyanoalkyl, or

R ^c and R ^d are taken together with the N to which they are attached to give a substituted or unsubstituted 4-12 membered heterocyclic ring or ring system with 0, 1, or 2 additional heteroaromatic ring atoms independently selected from N, O, and S where the rings in the heterocyclic ring system may be bridged, fused, spiro-fused, or any combination of the two; where any ring nitrogen atom of a heterocyclic ring or ring system is optionally quadric-covalent; and where the heterocyclic ring or ring system is optionally substituted with 1, 2, 3 or 4 substituents independently selected from

1) -(CH ₂ ) _0-3 halogen,

2) oxo,

3) =NH,

4) -(CH ₂ ) _0-3 OH,

5) -C _1-6 alkyl optionally substituted with halogen, -CN and -OH,

6) -OC _1-6 alkyl,

7) -CH ₂ CH (OH) CH ₂ NH ₂ ,

8) -CH ₂ CH(F)CH ₂ NH ₂ ,

9) -C(=O)OH,

10) -(CH ₂ ) _0-3 NR ^h R ^j , optionally substituted with 1 or 2-CH _3, -NH ₂ or halogen,

11) -NHCH ₂ CN,

12) -NHCH=NH,

13) -NHC(=O)R ⁱ ,

14) -NHC(=O)CH ₂ NHC(=NH)NH ₂ ,

15) -C (= NH) NH ₂ ,

16) -C(=O)C _1-6 aminoalkyl, optionally substituted with -OH,

17)-(CH₂)_0-2C(=O)(CH₂)_0-2NR^hR^j, optionally substituted-NH₂or -OH,

18) -(CH ₂ ) _0-2 C(=O)CH(NH ₂ )(CH ₂ ) _0-2 OH,

19) -C(=O)NH(CH₂)_1-3NH₂, optionally substituted -OH,

20) -C(=O)(CH₂)_1-3NH_2,optionally substituted -NH₂,

21) -C (= O) (CH ₂ ) _0-3 NHC (= NH) NH ₂ ,

22) -(CH ₂ ) _0-1 NHCH ₂ CH ₂ NR ^h R ^j ,

23) -(CH ₂ ) _0-3 NHC(=NH)NH ₂ ,

24) -(CH ₂ ) _0-1 NH(CH ₂ ) _0-1 C(=O)(CH ₂ ) _0-1 NR ^h R ^j ,

25) -(CH ₂ ) _0-1 NHSO ₂ (CH ₂ ) _0-2 NR ^h R ^j ,

26) -(CH ₂ ) _0-2 NHSO ₂ CH ₃ ,

27) -ONH ₂ ,

28) -ONHC(=O)CH ₂ NHCH ₃ ,

29) -C(=O)NH-pyridinyl,

30) -C(=O)- diazepinyl optionally substituted with -C(=N)NH ₂ ,

31) -C (= O) - piperazinyl,

32) -(CH ₂ ) _0-1 C(=O)- pyrrolidinyl, optionally substituted with -NH ₂ ,

33) -NHCH ₂ -pyridinyl optionally substituted with one or more groups selected from -CH ₃ , -OH and oxo,

34) -NH-pyrimidinyl,

35) -(CH ₂ ) _0-1 -phenyl,

36) -(CH ₂ ) _0-2 -piperazinyl,

37) -(CH ₂ ) _0-2 azetidinyl, optionally substituted with -NH ₂ , -CH ₂ NH ₂ , or -OH,

38) -(CH ₂ ) _0-2 pyrrolidinyl, optionally substituted with -NH ₂ ,

39) -(CH ₂ ) _0- triazolyl optionally substituted with -CH ₂ NH ₂ and

40) -(CH ₂ ) _0-2 tetrazolyl;

R ^f is H, -C(=O)N(C _1-6 alkyl) ₂ , -SO ₂ C _1-6 alkyl, -SO ₂ N(R ^x ) ₂ , -C(=O)-cyclopentyl- N(R ^x ) ₂ , -C(=O)- pyridinyl optionally substituted with one or more groups selected from oxo, -C ₁ - ₃ alkyl and -OH, -C(=O)- pyrrolidinyl substituted with -NR ^a R ^b or halogen, -C(=O)-thiazolidinyl, -SO ₂ -piperazine or -SO ₂ -pyrrolidinyl-N(R ^x ) ₂ ;

R ^g is hydrogen or C _1-3 alkyl, or

R ^f and R ^g are taken together with N, with which they are connected, receiving morpholinyl; piperazinil; pyrrolidinyl, optionally substituted with -CH ₃ ; piperidinyl or thiomorpholinyl, optionally substituted with -C _1-6 alkyl or -N(R ^x ) ₂ ; or triazolyl substituted with -CH ₂ NH ₂ ;

R ^h and R ^j are independently H, C _1-6 alkyl or C _3-8 cycloalkyl;

R ⁱ is -C _1-5 amino alkyl, -OC _1-6 alkyl, -C _1-3 cyanoalkyl or -C _1-6 haloalkyl optionally substituted with -NR ^x R ^y ;

R ^k is C _1-6 alkyl or thiazole substituted with -NH ₂ ;

each R ^x and R ^y is independently hydrogen or C _1-3 alkyl; and

where when HetA, AryA, AryC, HetC or the rings formed by the combination of R and R ⁰ are substituted, the substituents are 1-4 members selected from

1) halogen,

2) -OH,

3) oxo,

4) -COOH,

5) -COOC _1-6 alkyl,

6) C _1-6 alkyl,

7) C _1-6 alkoxy,

8) -(CH ₂ ) _0-3 OC _1-3 alkyl,

9) C _1-6 haloalkyl,

10) C _1-6 hydroxyalkyl,

11) C ₃ -C ₈ cycloalkyl,

12) -C(=O)C _1-6 alkyl,

13) -C(=O)C _1-6 aminoalkyl,

14) -C(=O)NR ^c R ^d ,

15) -(CH ₂ ) _0-1 NR ^x R ^y ,

16) -(CH ₂ ) _0-3 NR ^f R ^g ,

17) -(CH ₂ ) _1-3 -C(=O)NR ^x R ^y ,

18) -NHCH ₂ CN,

19) -NHC(=O)R ⁱ ,

20) -(CH ₂ ) _0-1 NHSO ₂ NR ^x R ^y ,

21) -SO ₂ NR ^c R ^d ,

22) -CH=NH,

23) -(CH ₂ ) _0-3 C(=NH)NH ₂ ,

24) -(CH ₂ ) _0-3 NHC(=NH)NH ₂ ,

25) -(CH ₂ ) _0-2 -thienyl,

26) -(CH ₂ ) _0-2 -tetrazolyl,

27) -(CH ₂ ) _0-2 -thiazolyl,

28)-(CH₂)_0-2-pyridinyl optionally substituted with -CH₃or quaternized -CH₃or CH₂CONH₂,

29) -(CH ₂ ) _0-2 -triazolyl,

30) -(CH ₂ ) _0-2 -piperidinyl, optionally substituted with -CH ₃ or quaternized with -CH ₃ or -(CH ₂ ) _0-3 NH _2,

31) -(CH ₂ ) _0-2 -pyrazolyl optionally substituted with one or more - (CH ₂ ) _0-3 NH ₂ and further optionally quaternized with -CH _3,

32) -(CH ₂ ) _1-3 -C(=O) -pyrrolidinyl optionally substituted with -NR ^x R ^y ,

33) -(CH ₂ ) _0-2 -pyrrolidinyl optionally substituted with -NR ^x R ^y ,

34) -C(=NH) -pyrrolidinyl optionally substituted with -NR ^x R ^y , and

35) 4,5-dihydrothiazol-2-yl.

The present invention also relates to compounds of formula (Ib)

(Ib)

(IB)

or their stereoisomer, internal salt, N-oxide, prodrug or pharmaceutically acceptable salt:

where:

A is -NR ⁰ R or -OR ^z ;

R ^z is isoxazolyl;

R ⁰ is hydrogen or C _1-6 alkyl which is optionally substituted with one or two substituents selected from halo, hydroxyl, cyano, carbamoyl, -SO ₂ NH ₂ and C _1-6 alkoxy;

R represents:

- (CH ₂ ) _n C(=O)R ² ;

- (CH ₂ ) _n C(=S)R ² ;

- (CH ₂ ) _n SO ₂ R ² ;

-C _1-6 alkyl optionally substituted with -C _3-6 cycloalkyl; or

-CH(=NH); or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S;

n is an integer selected from 0, 1, 2, 3, 4, 5 and 6;

R ¹ is:

1) -(CH ₂ ) _0-6 -AryC;

2) -(CH ₂ ) _0-6 -HetC; or

3) C _2-6 aminoalkyl optionally substituted with a) -C(=O)C _1-6 alkoxy, b) -C(=O)-pyrrolidinyl substituted with -NR ^x R ^y ,

c) -CR ^x =NR ^x , or

d) -COO-phenyl;

^R2 is:

H;

C_1-6alkyl optionally substituted with 1, 2 or 3 substituents independently selected from halo, -OH, -CN, C_3-8cycloalkyl, -(CH₂)_0-1C(=O)NR^xR^y, -NR^aR^b, C_1-6alkoxy, -OC(=O)C_1-6alkyl, -P(=O)(C_1-6alkoxy)₂, -COOH, -COOC_1-6alkyl, -SO₂C_1-6alkyl, -S(=O)C_1-6haloalkyl, AryA, -S-AryA and azetidinone optionally substituted with C_1-6hydroxyalkyl;

C _3-8 cycloalkyl substituted with C _1-6 haloalkyl or -NR ^x R ^y ;

-CR ^k =NOC _1-6 alkyl, optionally substituted-COOR ^x ;

-C(=O)NR ^x R ^y ;

-C(=O)C _1-6 alkoxy;

^{-NRxRy ;}

-OH;

-COOH;

C _1-6 alkoxy;

C _1-6 haloalkyl;

C _1-6 haloalkoxy;

AryA; or

HetA;

R^four represents-COO^-or -COOR⁵;

R ⁵ is hydrogen, a carboxylic acid protecting group, or an ester prodrug moiety;

AryA is 1) a substituted or unsubstituted 5- or 6-membered aromatic ring with 0, 1, 2, 3, or 4 heteroaromatic ring atoms independently selected from N, O, and S, or

2) a substituted or unsubstituted 9- or 10-membered bicyclic aromatic ring with 1, 2, 3, 4, 5 or 6 heteroaromatic ring atoms independently selected from N, O and S;

HetA is a substituted or unsubstituted 5-10 membered saturated ring with 1, 2, 3 or 4 heteroaromatic ring atoms independently selected from N, O and S, where any S atom in the ring is optionally oxidized;

AryC is 1) a substituted or unsubstituted 5- or 6-membered aromatic ring with 1, 2, or 3 heteroaromatic ring atoms independently selected from N, O, and S, or

2) a substituted or unsubstituted 7-10 membered bicyclic aromatic ring with 0, 1, 2 or 3 heteroaromatic ring atoms selected from N, S, and O;

HetC is a substituted or unsubstituted 4-6 membered saturated ring with 1 or 2 heteroaromatic ring atoms selected from N, O or S;

R ^a is hydrogen, C _1-6 alkyl, C _3-8 cycloalkyl, -CR ^x (=NR ^x ), -C(=NR ^x )N(R ^x ) ₂ , -CH ₂ C(=O)N (R ^x ) ₂ , or -SO ₂ C _1-6 alkyl;

R ^b is hydrogen or C _1-3 alkyl;

R^c is H; -C_1-6alkyl optionally substituted with -NR^hR^j,-CN or -OH; -(CH₂)_1-3C(=O)NR^xR^y; -(CH₂)_1-3C(=O)NHCH₂CH₂OH; -(CH₂)_1-3C(=O)NHOCH₃; -(CH₂)_1-3C(=O)NHOBn; -C_1-6alkoxy; pyridinyl; pyrrolidinyl, optionally substituted with -C(=O)NR^xR^y; tetrahydro-2H-pyran-4-yl; -(CH₂)_1-3C(=O)- diazepanil; -(CH₂)_1-3C(=O)-pyrrolidin-1-yl substituted with NR^xR^y; -(CH₂)_1-3-pyranyl optionally substituted with 1 or 2 substituents selected from oxo and methoxy; -(CH₂)_1-3-pyridinyl optionally substituted with one or more groups selected from -CH₃, -OH, and oxo; or -phenyl-C(=O)-pyrrolidinyl-NR^xR^y _;

R ^d is hydrogen, C _1-3 alkyl, C _1-3 hydroxyalkyl or C _1-3 cyanoalkyl; or

R ^c and R ^d are taken together with the N to which they are attached to give a substituted or unsubstituted 4-12 membered heterocyclic ring or ring system with 0, 1 or 2 additional heteroaromatic ring atoms independently selected from N, O, and S, where the rings in the heterocyclic ring system may be bridged, fused, spiro-fused, or any combination of the two; where any ring nitrogen atom of a heterocyclic ring or ring system is optionally quadric-covalent; and where the heterocyclic ring or ring system is optionally substituted with 1, 2, 3 or 4 substituents independently selected from

halogen;

oxo;

-OH;

-C _1-6 alkyl optionally substituted with -OH, halogen or cyano;

-CH ₂ CH(OH)CH ₂ NH ₂ ;

-C(=O)OH;

- (CH ₂ ) _0-3 NR ^h R ^j , optionally substituted with -NH ₂ or halogen;

-NHCH ₂ CN;

-NHCH=NH;

-NHC(=O)R ⁱ ;

-NHC(=O)CH ₂ NHC(=NH)NH ₂ ;

-C(=NH)NH ₂ ;

-C(=O)C _1-6 aminoalkyl optionally substituted with -OH;

-(CH ₂ ) _0-2 C(=O)(CH ₂ ) _0-2 NR ^h R ^j ;

-(CH ₂ ) _0-2 C(=O)CH(NH ₂ )(CH ₂ ) _0-2 OH;

-C(=O)(CH ₂ ) _0-3 NHC(=NH)NH ₂ ;

-(CH ₂ ) _0-1 NHCH ₂ CH ₂ NR ^h R ^j ;

-(CH ₂ ) _0-3 NHC(=NH)NH ₂ ;

-(CH ₂ ) _0-1 NH(CH ₂ ) _0-1 C(=O)(CH ₂ ) _0-1 NR ^h R ^j ;

-(CH ₂ ) _0-1 NHSO ₂ (CH ₂ ) _0-2 NR ^h R ^j ;

-(CH ₂ ) _0-2 NHSO ₂ CH ₃ ;

-ONH ₂ ;

-ONHC(=O)CH ₂ NHCH ₃ ;

-C(=O)NH-pyridinyl;

-C(=O)-piperazinyl;

-C(=O)- pyrrolidinyl optionally substituted with -NH ₂ ;

-NHCH ₂ -pyridinyl optionally substituted with one or more groups selected from -CH3, -OH and oxo;

-NH-pyrimidinyl;

-(CH ₂ ) _0-1 -phenyl;

-(CH ₂ ) _0-2 -piperazinyl;

-(CH ₂ ) _0-2 azetidinyl optionally substituted with -NH ₂ , -CH ₂ NH ₂ , or -OH;

-(CH ₂ ) _0-2 pyrrolidinyl optionally substituted with -NH ₂ ;

-(CH ₂ ) ₀ -triazolyl optionally substituted with -CH ₂ NH ₂ ; and

-(CH ₂ ) _0-2 tetrazolyl;

^Rf is H; -C(=O)N(C _1-6 alkyl) ₂ ; -SO ₂ C _1-6 alkyl; -SO ₂ N(R ^x ) ₂ ; -C(=O)-cyclopentyl-N(R ^x ) ₂ ; -C(=O)-pyridinyl optionally substituted with one or more groups selected from oxo, -C _{1 -3} alkyl and -OH; -C(=O)-pyrrolidinyl substituted with -NR ^a R ^b or halogen; -C(=O)-thiazolidinyl; -SO ₂ -piperazine or -SO ₂ -pyrrolidinyl-N(R ^x ) ₂ ;

R ^g is hydrogen or C _1-3 alkyl; or

R ^f and R ^g are taken together with N, with which they are connected, receiving morpholinyl; piperazinil; pyrrolidinyl, optionally substituted with -CH ₃ ; piperidinyl or thiomorpholinyl, optionally substituted with -C _1-6 alkyl or -N(R ^x ) ₂ ; or triazolyl substituted with -CH ₂ NH ₂ ;

R ^h and R ^j are independently H, C _1-6 alkyl or C _3-8 cycloalkyl; R ⁱ is -C _1-5 aminoalkyl; -OC _1-6 alkyl; -C _1-3 cyanoalkyl; or -C _1-6 haloalkyl optionally substituted with -NR ^x R ^y ;

R ^k is C _1-6 alkyl or thiazole substituted with -NH ₂ ;

each R ^x and R ^y is independently hydrogen or C _1-3 alkyl;

where when HetA, AryA, AryC, HetC or the rings formed by the combination of R and R ⁰ are substituted, the substituents are 1-4 members selected from

halogen;

-OH;

oxo;

-COOH;

-COOC _1-6 alkyl;

C _1-6 alkyl;

C _1-6 alkoxy;

-(CH ₂ ) _0-3 OC _1-3 alkyl;

C _1-6 haloalkyl;

C _1-6 hydroxyalkyl;

C ₃ -C ₈ cycloalkyl;

-C(=O)C _1-6 alkyl;

-C(=O)C _1-6 aminoalkyl;

-C(=O)NR ^c R ^d ;

-(CH ₂ ) _0-3 NR ^f R ^g ;

-NHCH ₂ CN;

-NHC(=O)R ⁱ ;

-(CH ₂ ) _0-1 NHSO ₂ NR ^x R ^y ;

-SO ₂ NR ^c R ^d ; -CH=NH;

-(CH ₂ ) _0-2 -thienyl;

-(CH ₂ ) _0-2 -tetrazolyl;

-(CH ₂ ) _0-2 -thiazolyl;

-(CH ₂ ) _0-2 -pyridinyl, optionally substituted with -CH ₃ or quaternized with -CH ₃ ;

-(CH ₂ ) _0-2 -triazolyl; and

4,5-dihydrothiazol-2-yl.

The present invention also relates to a compound of formula (Ia), or a stereoisomer, internal salt, N-oxide or pharmaceutically acceptable salt thereof, wherein

( ia )

where:

A is NR ⁰ R or -triazolyl substituted with -CH ₂ OH;

R represents:

-C(=O)-C _1-6 alkyl-NR ^a R ^b ;

-C(=O)CHF ₂ ;

-C(=O)CH ₂ SCHF ₂ ,

-C (= O) CH ₂ NH (CH ₂ ) ₂ OMe,

-C(=O)CH ₂ pyrrolidine,

-C(=O)CH ₂ azetidine,

-C(=O)CH ₂ piperazine,

-C(=O)CH₂pyrrolidine, optional substituted with 1 or 2 substituents selected from fluoro and -CH₂NHMe,

-C(=O)CH ₂ -tetrazole optionally substituted with -C(CH ₃ ) ₃ , -CF ₃ , -CHF ₂ , -CH ₃ , -NH ₂ -COOC _1-6 alkyl, thienyl, -CH ₂ NHCH ₃ , -NH ₂ or -COOCH ₂ CH ₃ ; or -SO ₂ CH ₃ ;

R ⁰ is H;

R ¹ is pyrrolidinyl substituted with 1 or 2 -CONR ^c R ^d ; -CH ₂ NHSO ₂ NH ₂ or -CH ₂ -pyrrolidinyl optionally substituted with -NH ₂ ;

R ^a and R ^b are independently H, -C _1-6 alkyl, -C _3-8 cycloalkyl, -SO ₂ CH ₃ , -CH(=NH), -C(=NH)NH ₂ or -CH ₂ C (=O)NH ₂ ;

R ^c and R ^d are independently H, C _1-3 alkyl, -C(=NH)-pyrrolidinyl, optionally substituted with -NH ₂ or

R ^c and R ^d are taken together with the N to which they are attached to give a 4-12 membered heterocyclic ring or ring system with 0, 1, 2 or 3 additional heteroaromatic ring atoms selected from N and O; where any ring nitrogen atom of a heterocyclic ring or ring system is optionally quadric-covalent; the ring system is a bridged, fused or spiro ring system; and the 4-12 membered heterocyclic ring or ring system is optionally substituted with 1, 2 or 3 substituents selected from

(=NH),

-C (= O) (CH ₂ ) _1-2 NH ₂ ,

-C(=O)CH ₂ NHCH ₃ ,

-CH ₂ CH (NH ₂ ) CH ₂ NH ₂ ,

-C (= O)CH (NH ₂ )CH ₂ NH ₂ ,

-C (= O) CH (F) CH ₂ NH ₂ ,

-C(=O)CH(NH ₂ )CH ₂ OH,

-CH ₂ CH (OH) CH ₂ NH ₂ ,

-C (= O) NH CH ₂ CH (OH) CH ₂ NH ₂ ,

-C(=NH)NH ₂ ,

-COOH,

_-CH3 ,

-CH ₂ C (= O) NH ₂ ,

-CH ₂ NH CH ₂ C (= O) NH ₂ ,

-CH ₂ NR ^h R ^j ,

-CH ₂ CH ₂ NH ₂ ,

-CH ₂ CH ₂ NH-C (= NH) -NH ₂ ,

-CH ₂ NHSO ₂ NH ₂ ,

_-CH2OH ,

-C(CH ₃ ) ₂ NH ₂ ,

-CH ₂ F,

-OH,

-OMe,

-F,

-NR ^h R ^j ,

-NHCH=NH,

-NH-C(=NH)-NH ₂ ,

-NHCOCH ₂ -NH-C (= NH) -NH ₂ ,

-NHCOCH ₂ NH ₂ ;

-(CH ₂ ) _0-3 NR ^h R ^j , optionally substituted with -NH ₂ or halogens;

Azetidinyl, optionally substituted with -OH,

piperazinil and

Triazolyl substituted with CH ₂ NH ₂ ; and

R ^h and R ^j are independently H, C _1-6 alkyl or C _3-8 cycloalkyl.

Any of the combinations of A, X, Z, R ¹ and R ⁴ are included herein and are specifically represented by the present invention.

In another aspect, described in the present invention is also a pharmaceutical composition containing a compound of formula (I), (Ia) or (Ib) or its stereoisomer, pharmaceutically acceptable salt or N-oxide.

In another aspect, the compounds described in the present invention can also be combined with suitable β-lactamase inhibitors, increasing the spectrum of antibiotic activity. In another aspect, the compounds described in the present invention can also be combined with suitable dehydropeptidase inhibitors.

In another aspect, described in the present invention is a method for obtaining compounds of formula (I), (Ia) or (Ib), or its stereoisomer, pharmaceutically acceptable salt or N-oxide.

In another aspect, the present invention also provides a method for preventing or treating a bacterial infection, comprising administering a therapeutically effective amount of a compound of formula (I), (Ia) or (Ib) or a stereoisomer thereof, a pharmaceutically acceptable salt, a pharmaceutical composition, or an N-oxide.

In another aspect, the present invention also provides a method for preventing or treating a gram-positive and/or gram-negative bacterial infection, comprising administering a therapeutically effective amount of a compound of formula (I), (Ia) or (Ib) or a stereoisomer thereof, a pharmaceutically acceptable salt, a pharmaceutical composition or N-oxide.

In another aspect, the present invention also provides a method for preventing or treating a bacterial infection, comprising administering a therapeutically effective amount of a compound of formula (I), (Ia) or (Ib), in combination or in alternation with one or more other antimicrobial agents.

Embodiments, sub-embodiments, aspects and features of the present invention are either described hereinafter in or will be understood from the following description, examples and the appended claims.

Detailed description

The present invention is based in part on the discovery of carbapenem derivatives that are bactericidal against a wide range of bacteria.

In a first embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib) as described above, or a stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt thereof.

In a second embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt thereof, wherein A is -NR ⁰ R and the other groups are itself, as represented in the general formula of formula (I), (Ia) or (Ib).

In another embodiment, A is -NR ⁰ R. In another embodiment, X is -S-. In another embodiment, Z is -CH ₃

In a third embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt thereof, wherein

R ⁰ is hydrogen or methyl;

R represents

-(CH ₂ ) _n C(=O)R ² ; or

-(CH ₂ ) _n SO ₂ R ² ; or

R and R ⁰ , together with the N to which they are connected, form

1) [1,2,3]triazolyl substituted with C _1-6 alkyl, where C _1-6 alkyl is substituted with halogen, -NR ^a R ^b , -OH or C _1-3 alkoxy; or

2) tetrazolyl, optionally substituted with -NR ^a R ^b ; and other groups are as represented in the general formula of formula (I), (Ia) or (Ib) above or in the embodiments.

In another embodiment, R ⁰ is hydrogen or methyl;

R represents

-(CH ₂ ) _n C(=O)R ² ; or

-(CH ₂ ) _n SO ₂ R ² ; or

R and R ⁰ , together with the N to which they are connected, form

1) [1,2,3]triazolyl substituted with C _1-6 alkyl, where C _1-6 alkyl is substituted with halogen, -NR ^a R ^b , -OH, or C _1-3 alkoxy; or

2) tetrazolyl, optionally substituted with -NR ^a R ^b .

In a fourth embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib) or a stereoisomer, internal salt, N-oxide or pharmaceutically acceptable salt thereof, wherein n is 0 or 1 and the other groups are, as represented in the general formula of formula (I), (Ia) or (Ib), above or in the embodiments. In one aspect of this embodiment, n is 0.

In another embodiment, n is 0 or 1. In one aspect of this embodiment, n is 0.

In a fifth embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib) or a stereoisomer, internal salt, N-oxide or pharmaceutically acceptable salt thereof, wherein R ¹ is: -(CH ₂ ) _{0- 2} -AryC or -(CH ₂ ) _0-1 -HetC, and other groups are as represented in the general formula of formula (I), (Ia) or (Ib) above or any of the embodiments.

In another embodiment, R ¹ is -(CH ₂ ) _0-2 -AryC or -(CH ₂ ) _0-1 -HetC.

In another embodiment, R ⁴ is -COOH.

In a sixth embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt thereof, wherein

AryA represents

1) 5-6 membered aromatic ring with 0, 1, 2, 3 or 4 heteroaromatic ring atoms independently selected from N, O and S, optionally substituted with 1 or 2 substituents independently selected from halogen, C _1-6 alkyl, C _1-6 haloalkyl, -(CH ₂ ) _0-1 NR ^x R ^y , C ₃ -C ₈ cycloalkyl, -COOH, -COOC _1-6 alkyl, C _1-6 alkoxy, thienyl and tetrazolyl, or

2) a 9-10 membered bicyclic aromatic ring with 1-6 heteroaromatic ring atoms independently selected from N, O and S, optionally substituted with 1 or 2 substituents selected from halogen, C _1-6 alkyl and C _1-6 haloalkyl;

HetA is a 5-10 membered saturated ring with 1 or 2 heteroaromatic ring atoms independently selected from N, O and S, optionally substituted with 1 or 2 substituents independently selected from halogen, -NR ^x R ^y , -CH ₂ NR ^x R ^y , -OH and oxo;

AryC is 1) a 5- or 6-membered aromatic ring with 0, 1 or 2 heteroaromatic ring atoms independently selected from N and S, optionally quaternized with CH ₃ and optionally substituted with 1-3 substituents independently selected from -CH ₂ NR ^x R ^y , -CH ₂ -pyrrolidinyl, -OH, oxo, pyridinyl, which is optionally methyl quaternized or -CH ₂ CONH ₂ , or

3) 7-10 membered bicyclic aromatic ring with 3 heteroaromatic ring atoms selected from N; and

HetC is a 4-8 membered saturated ring with 1 or 2 N or O ring atoms optionally substituted with 1 or 2 substituents independently selected from halo, -OH, -C_1-6alkyl,-(CH₂)_0-3NR^fR^g, -CH=NH, -C(=O)C_1-6alkyl, -C(=NH)-NH₂, -CH₂- (C=O) -pyrrolidinyl optionally substituted with -NR^xR^y, -NH-C(=NH) -NH₂, -CH₂-NH-C(=NH) -NH₂, -C(=O)C_1-6aminoalkyl, -C(=O)NR^cR^d, -NR^xR^y, -NHSO₂NR^xR^y, -SO₂NR^cR^d, thiazolyl and 4,5-dihydrothiazol-2-yl; and other groups are as represented in the general formula of formula (I), (Ia) or (Ib) above or any of the embodiments.

In another embodiment, AryA is 1) a 5-6 membered aromatic ring with 0, 1, 2, 3, or 4 heteroaromatic ring atoms independently selected from N, O, and S, optionally substituted with 1 or 2 substituents independently selected from halogen, C _1-6 alkyl, C _1-6 haloalkyl, -(CH ₂ ) _0-1 NRxRy, C ₁ -C ₆ cycloalkyl, -COOH, -COOC _1-6 alkyl, C _1-6 alkoxy, thienyl and tetrazolyl ; or

2) a 9-10 membered bicyclic aromatic ring with 1-6 heteroaromatic ring atoms independently selected from N, O and S, optionally substituted with 1 or 2 substituents selected from halogen, C _1-6 alkyl and C _1-6 haloalkyl;

HetA is a 5- or 6-membered saturated ring with 1 or 2 heteroaromatic ring atoms independently selected from N, O and S, optionally substituted with 1 or 2 substituents independently selected from halo, -NR ^x R ^y , -OH and oxo ;

AryC is

1) 5- or 6-membered aromatic ring with 1 or 2 heteroaromatic ring atoms independently selected from N and S, optionally substituted with 1-3 substituents independently selected from -CH ₂ NR ^x R ^y , - OH, oxo, pyridinyl, which is optionally quaternized with methyl; or

2) an 8-membered bicyclic aromatic ring with 3 heteroaromatic ring atoms selected from N; and

HetC is a 4-6 membered saturated ring with 1 or 2 N ring atoms, optionally substituted with 1 or 2 substituents independently selected from halogen; -C _1-6 alkyl optionally substituted with -NR ^f R ^g ; -CH=NH; -C(=O)C _1-6 alkyl; -C(=O)C _1-6 aminoalkyl; -C(=O)NR ^c R ^d ; ^{-NRxRy ;} -NHSO ₂ NR ^x R ^y ; -SO ₂ NR ^c R ^d ; thiazolyl and 4,5-dihydrothiazol-2-yl.

In a seventh embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt thereof, wherein:

^Rc represents

1) H

2) -CH ₂ CN,

3) -C _1-6 alkyl optionally substituted with -NR ^h R ^j , pyrrolidinyl or -OH,

4) -CH ₂ CH ₂ C (= O) NR ^x R ^y ,

5) -CH ₂ CH ₂ C (= O) NHCH ₂ CH ₂ OH,

6) -CH ₂ CH ₂ C (= O) NHOCH _3,

7) -CH ₂ CH ₂ C (= O) NHOBn,

8) -C _1-6 alkoxy,

9) pyridinyl,

10) pyrrolidinyl, optionally substituted with -C(=O)NR ^x R ^y ,

11) -C(=NH)- pyrrolidin-1-yl, optionally substituted with NR ^x R ^y ,

12) tetrahydro-2H-pyran-4-yl,

13) -CH ₂ CH ₂ C (= O) - diazepanil,

14) -CH ₂ CH ₂ C (= O) - pyrrolidin-1-yl, substituted with NR ^x R ^y ,

15) -CH ₂ -pyranyl optionally substituted with 1 or 2 substituents selected from oxo and methoxy,

16) -CH ₂ -pyridinyl, optionally substituted with -CH ₃ , -OH and oxo,

17) -phenyl-C(=O)-piperazinyl,

18) -phenyl-CH ₂ -NR ^x R ^y or

19) -phenyl-C(=O)-pyrrolidinyl-NR ^x R ^y _;

R ^d is hydrogen or C _1-3 alkyl; or

R ^c and R ^d are taken together with the N to which they are connected, getting

a) a 4-8 membered heterocyclic ring with 0, 1 or 2 additional heteroaromatic ring atoms independently selected from N, O, and S, or

b) a 6-12 membered heterocyclic bi- or tricyclic ring with 0, 1 or 2 additional heteroaromatic ring atoms independently selected from N, O, and S, where the bicyclic ring is optionally bridged, fused or spirocyclic, or any combination of two

and where any ring nitrogen atom of the heterocyclic ring or heterocyclic bicyclic ring is optionally quadric-covalent; and where the heterocyclic ring or heterocyclic bicyclic ring is optionally substituted with 1, 2 or 3 substituents independently selected from

1) halogen,

2) -C _1-6 alkyl optionally substituted with 1 or 2 substituents selected from halo, -CN and -OH,

3) -C (= NH) NH ₂ ,

4)-(CH₂)_0-2C(=O)(CH₂)_0-2NR^hR^j, optionally substituted-NH₂or -OH,

5) -(CH ₂ ) _0-3 NR ^h R ^j , optionally substituted-NH ₂ or halogen,

6) -C(=O)C _1-6 aminoalkyl, optionally substituted with -OH,

7) -C(=O)OH,

8) -C (= O) (CH ₂ ) _0-3 NHC (= NH) NH ₂ ,

9) -(CH ₂ ) _0-1 NHCH ₂ CH ₂ NR ^h R ^j ,

10) -(CH ₂ ) _0-3 NHC(=NH)NH ₂ ,

11) -(CH ₂ ) _0-1 NH(CH ₂ ) _0-1 C(=O)(CH ₂ ) _0-1 NR ^h R ^j ,

12) -(CH ₂ ) _0-1 NHSO ₂ NH ₂ ,

13) -(CH ₂ ) _0-1 NHSO ₂ (CH ₂ ) _0-2 NH ₂ ,

14) -(CH ₂ ) _0-2 NHSO ₂ CH ₃ ,

15) -NR ^h R ^j ,

16) -NHCH ₂ CN,

17) -NHCH=NH,

18) -NHC(=O)R ⁱ ;

19) -NHSO ₂ N(CH ₃ ) ₂ ,

20) -NHC(=O)(CH ₂ ) _0-2 NH(=NH)NH ₂ ,

21) -OH,

22) -OC _1-6 alkyl,

23) -ONH ₂ ,

24) -ONHC(=O)CH ₂ NHCH ₃ ,

25) oxo,

26) =NH,

27) -(CH ₂ ) _0-1 -phenyl,

28) -(CH ₂ ) _0-2 -piperazinyl,

29) -C(=O)NH-pyridinyl,

30) -C (= O) - piperazinyl,

31) -C(=O)- pyrrolidinyl, optionally substituted with -NH ₂ ,

32) Azetidinyl, optionally substituted with -CH ₂ NH ₂ , -NH ₂ or -OH,

33) Pyrrolidinyl, optionally substituted with -NH ₂ ,

34) -NHCH ₂ -pyridinyl substituted with oxo, -CH ₃ , and -OH,

35) -NH-pyrimidinyl,

36) Triazolyl, optionally substituted with -CH ₂ NH ₂ and

37) tetrazolyl;

and other groups are as represented in the general formula of formula (I), (Ia) or (Ib) above or any of the embodiments.

In another embodiment, R^c is H; -CH₂CN; -C_1-6alkyl optionally substituted with -NR^hR^j or -OH; -CH₂CH₂C(=O)NR^xR^y; -CH₂CH₂C(=O)NHCH₂CH₂OH; -CH₂CH₂C(=O)NHOCH₃; -CH₂CH₂C(=O)NHOBn; -C_1-6alkoxy; pyridinyl; pyrrolidinyl, optionally substituted with -C(=O)NR^xR^y; tetrahydro-2H-pyran-4-yl; -CH₂CH₂C(=O)- diazepanil; -CH₂CH₂C(=O)-pyrrolidin-1-yl substituted with NR^xR^y; -CH₂-pyranyl optionally substituted with 1 or 2 substituents selected from oxo and methoxy; -CH₂-pyridinyl optionally substituted with -CH₃, -OH, and oxo; or -phenyl-C(=O)-pyrrolidinyl-NR^xR^y _;

R ^d is hydrogen or C _1-3 alkyl; or

R ^c and R ^d are taken together with the N to which they are connected, getting

a) a 4-8 membered heterocyclic ring with 0, 1 or 2 additional heteroaromatic ring atoms independently selected from N, O, and S; or

b) a 6-12 membered heterocyclic bicyclic ring with 0, 1 or 2 additional heteroaromatic ring atoms independently selected from N, O, and S, where the bicyclic ring is optionally bridged, fused or spirocyclic, or any combination of the two;

and where any ring nitrogen atom of the heterocyclic ring or heterocyclic bicyclic ring is optionally quadric-covalent; and where the heterocyclic ring or heterocyclic bicyclic ring is optionally substituted with 1 or 2 substituents independently selected from

halogen;

-C _1-6 alkyl optionally substituted with 1 or 2 substituents selected from halo, -CN, -NR ^h R ^j and -OH;

-C(=NH)NH ₂ ;

- (CH ₂ ) _0-2 C(=O)(CH ₂ ) _0-2 NR ^h R ^j ;

- (CH ₂ ) _0-3 NR ^h R ^j , optionally substituted with -NH ₂ or halogen;

-C(=O)C _1-6 aminoalkyl optionally substituted with -OH;

-C(=O)OH;

-C(=O)(CH ₂ ) _0-3 NHC(=NH)NH ₂ ;

- (CH ₂ ) _0-1 NHCH ₂ CH ₂ NR ^h R ^j ;

- (CH ₂ ) _0-3 NHC(=NH)NH ₂ ;

- (CH ₂ ) _0-1 NH(CH ₂ ) _0-1 C(=O)(CH ₂ ) _0-1 NR ^h R ^j ;

- (CH ₂ ) _0-1 NHSO ₂ NH ₂ ;

- (CH ₂ ) _0-1 NHSO ₂ (CH ₂ ) _0-2 NH ₂ ;

- (CH ₂ ) _0-2 NHSO ₂ CH ₃ ;

-NR ^h R ^j ;

-NHCH ₂ CN;

-NHCH=NH;

-NHC(=O)R ⁱ ;

-NHSO ₂ N(CH ₃ ) ₂ ;

-OH;

-ONH ₂ ;

-ONHC(=O)CH ₂ NHCH ₃ ;

oxo;

- (CH ₂ ) _0-1 -phenyl;

- (CH ₂ ) _0-2 -piperazinyl;

-C(=O)NH-pyridinyl;

-C(=O)-piperazinyl;

-C(=O)- pyrrolidinyl optionally substituted with -NH ₂ ;

Azetidinyl optionally substituted with -CH ₂ NH ₂ , -NH ₂ , or -OH;

Pyrrolidinyl, optionally substituted with -NH ₂ ;

-NHCH ₂ -pyridinyl substituted with oxo, -CH ₃ and -OH;

-NH-pyrimidinyl;

Triazolyl, optionally substituted with -CH ₂ NH ₂ ; and

tetrazolyl.

In a sixth embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt thereof, wherein:

R ⁰ is hydrogen, and R is:

1) -C(=O)CHF ₂ ,

2) -C (= O) CF ₃ ,

3) -C(=O)CH ₂ CF ₃ ,

4) -C (= O) CF ₂ CF ₃ ,

5) -C(=O)CF ₂ -C _1-6 alkyl,

6) -C(=O)CHFCH ₃ ,

7) -C (= O) CF ₂ CH ₂ NH ₂ ,

8) -C (= O) CF ₂ CH ₂ OH,

9) -C (= O) CH ₂ OH,

10) -C(=O)CH ₂ OCOCH ₃ ,

11) -C (= O) CH ₂ CN,

12) -C (= O) CH ₂ SO ₂ C _1-6 alkyl _,

13) -C(=O)CH ₂ SCHF ₂ ,

14) -C(=O)CH ₂ S(=O)CHF _2,

15) -C(=O)CH ₂ P(=O)(OCH ₃ ) _2,

16) -C(=O)CH ₂ S-tetrazole, optionally substituted with -CH ₃ ,

17) -C (= O) CH ₂ -thienyl,

18) -C (= O) CH (NH ₂ ) CH ₂ -tetrazole,

19) -C (= O) CH (NH ₂ ) CH ₂ -pyrazole,

20) -C(=O)CH ₂ -tetrazole optionally substituted with -C(CH ₃ ) ₃ , -CF ₃ , -CHF ₂ , -CH ₃ , NH ₂ -COOC _1-6 alkyl, thienyl, -CH ₂ NHCH ₃ , -NH ₂ , or -COOEt,

21) -C(=O)CH ₂ -triazole, optionally substituted with -CH ₂ NR ^a R ^b or -CH ₃ and -CF ₃ or -CF ₃ and -NH ₂ ,

22) -C (= O) CH ₂ -oxadiazole-CH ₂ NR ^a R ^b ,

23) -C (= O) C (CH ₃ ) ₂ -tetrazole,

24) -C (= O) CH ₂ -azetidine,

25) -C(=O)CH(CH ₃ )-azetidine optionally substituted with oxo, hydroxyethyl or both,

26) -C(=O)CH ₂ -pyrrolidinyl optionally substituted with one or more -F or -CH ₂ NHCH ₃ ,

27) -C (= O) CF ₂ -thienyl,

28) -C(=O)- C _1-6 alkyl-NR ^a R ^b ,

29) -C(=O)- pyrrolidinyl, optionally substituted with F or NH ₂ ,

30) -C (= O) - tetrahydrofuran,

31) -C(=O)- (CH ₂ ) _0-1 piperazine,

32) -C (= O) - pyrazine,

33) -C(=O)-thiazolidine, optionally substituted with one or more oxo,

34) -C(=O)- pyrazole, optionally substituted with CH ₃ and CF ₃ ,

35) -C(=O)CH(NH ₂ )C _1-6 alkyl, optionally substituted with -OH or phenyl,

36) -C(=O)CHFC _1-6 alkyl,

37) -C(=O)CH(OH)C _1-6 alkyl,

38) -C (= O) CR ^k \u003d NOC (CH ₃ ) ₂ COOH,

39) -C(=O)CR ^k =NOCH ₃ ;

40) -C(=S)OC _1-6 alkyl,

41) -C(=O)C(=O)OH,

42) -C(=O)C(=O)NR ^a R ^b ,

43) -C(=O)(CH ₂ ) _1-6 C(=O)NR ^a R ^b ,

44) -C(=O)C(=O)ONR ^a R ^b ,

45) -C(=O)C(=O)OC _1-6 alkyl,

46) -(CH ₂ ) _0-6 C(=O)OH,

47) -(CH ₂ ) _0-6 C(=O)OC _1-6 alkyl,

48) -(CH ₂ ) _0-6 C(=O)(CH ₂ ) _1-6 OH,

49) -(CH ₂ ) _0-6 C(=O)(CH ₂ ) _1-6 OC _1-6 alkyl,

50) -C (= O) OCH ₂ CHF ₂ ,

51) -C (= O) OCH ₂ CF ₃ ,

52) -C(=O)-C_3-6cycloalkyl substituted with CF₃or NH₂,

53) -C _1-6 alkyl-NR ^a R ^b ,

54) -C _1-6 alkyl-C _3-6 cycloalkyl,

55) -(CH ₂ ) _0-6 SO ₂ (CH ₂ ) _0-4 R ^e ,

56) -CH(=NH) or

57) -C _1-6 alkyl, or

R and R ⁰ , together with the N to which they are attached, form a [1,2,3-]triazole, optionally substituted with -CH ₂ OH, -CH ₂ OCH ₃ , -CH ₂ F, -CH ₂ NH ₂ , - CH ₂ NHCH ₃ , -C(=O)OCH ₃ or tetrazole optionally substituted with -NH ₂ ; and other groups are as represented in the general formula of formula (I), (Ia) or (Ib).

In another embodiment, R ⁰ is hydrogen and R is:

-C(=O)CHF ₂ ;

-C(=O)CF ₃ ;

-C(=O)CH ₂ CF ₃ ;

-C(=O)CF ₂ CF ₃ ;

-C(=O)CF ₂ -C _1-6 alkyl;

-C(=O)CHFCH ₃ ;

-C(=O)CF ₂ CH ₂ NH ₂ ;

-C(=O)CF ₂ CH ₂ OH;

-C(=O)CH ₂ OH;

-C(=O)CH ₂ OCOCH ₃ ;

-C(=O)CH ₂ CN;

-C(=O)CH ₂ SO ₂ C _1-6 alkyl _;

-C(=O)CH ₂ S(=O)CHF ₂ ;

-C(=O)CH ₂ P(=O)(OCH ₃ ) ₂ ;

-C(=O)CH ₂ S-tetrazole, optionally substituted with -CH ₃ ;

-C(=O)CH ₂ -thienyl;

-C(=O)CH(NH ₂ )CH ₂ -tetrazole;

-C(=O)CH(NH ₂ )CH ₂ -pyrazole;

-C(=O)CH ₂ -tetrazole optionally substituted with -C(CH ₃ ) ₃ , -CF ₃ , -CHF ₂ , -CH ₃ , NH ₂ -COOC _1-6 alkyl, thienyl, -CH ₂ NHCH ₃ , -NH ₂ or -COOEt;

-C(=O)CH ₂ triazole optionally substituted with -CH ₂ NR ^a R ^b or -CH ₃ and -CF ₃ or -CF ₃ and -NH ₂ ;

-C(=O)CH ₂ -oxadiazole-CH ₂ NR ^a R ^b ;

-C(=O)C(CH ₃ ) ₂ -tetrazole;

-C(=O)CH(CH ₃ )-azetidine optionally substituted with oxo, hydroxyethyl, or both;

-C(=O)CF ₂ -thienyl;

-C(=O)-C _1-6 alkyl-NR ^a R ^b ;

-C(=O)-pyrrolidinyl optionally substituted with F or NH ₂ ;

-C(=O)-tetrahydrofuran;

-C(=O)-piperazine;

-C(=O)-pyrazine;

-C(=O)-thiazolidine optionally substituted with one or more oxo;

-C(=O)- pyrazole optionally substituted with CH ₃ and CF ₃ ;

-C(=O)CH(NH ₂ )C _1-6 alkyl optionally substituted with -OH or phenyl;

-C(=O)CHFC _1-6 alkyl;

-C(=O)CH(OH)C _1-6 alkyl;

-C(=O)CR ^k =NOC(CH ₃ ) ₂ COOH;

-C(=O)CR ^k =NOCH ₃ ;

-C(=S)OC _1-6 alkyl;

-C(=O)C(=O)OH;

-C(=O)C(=O)NR ^a R ^b ;

-C(=O)(CH ₂ ) _1-6 C(=O)NR ^a R ^b ;

-C(=O)C(=O)ONR ^a R ^b ;

-C(=O)C(=O)OC _1-6 alkyl;

- (CH ₂ ) _0-6 C(=O)OH;

- (CH ₂ ) _0-6 C(=O)OC _1-6 alkyl;

- (CH ₂ ) _0-6 C(=O)(CH ₂ ) _1-6 OH;

- (CH ₂ ) _0-6 C(=O)(CH ₂ ) _1-6 OC _1-6 alkyl;

-C(=O)OCH ₂ CHF ₂ ;

-C(=O)OCH ₂ CF ₃ ;

-C(=O)-C_3-6cycloalkyl substituted with CF₃or NH₂;

-C _1-6 alkyl-NR ^a R ^b ;

-C _1-6 alkyl-C _3-6 cycloalkyl;

- (CH ₂ ) _0-6 SO ₂ (CH ₂ ) _0-4 R ^e ;

-CH(=NH); or

-C _1-6 alkyl; or

R and R ⁰ , together with the N to which they are attached, form a [1,2,3-]triazole, optionally substituted with -CH ₂ OH, -CH ₂ OCH ₃ , -CH ₂ F, -CH ₂ NH ₂ , - CH ₂ NHCH ₃ or -C(=O)OCH ₃ ; or tetrazole, optionally substituted with -NH ₂ .

In another embodiment, R ⁰ is hydrogen or C _1-6 alkyl which is optionally substituted with one or two substituents selected from halo, hydroxyl, cyano, carbamoyl, -SO ₂ NH ₂ and C _1-6 alkoxy;

R represents:

1) -(CH ₂ ) _n C(=O)R ² , or

2) -(CH ₂ ) _n SO ₂ R ² , or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S.

In another embodiment, R ⁰ is hydrogen or C _1-6 alkyl which is optionally substituted with one or two substituents selected from halo, hydroxyl, cyano, carbamoyl, -SO ₂ NH ₂ and C _1-6 alkoxy;

R represents:

1) -(CH ₂ ) _n C(=S)R ² ,

2) -C _1-6 alkyl optionally substituted with -C _3-6 cycloalkyl, or

3) -CH(=NH), or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S.

In a ninth embodiment, the present invention provides a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide or pharmaceutically acceptable salt thereof, wherein R ⁰ is hydrogen and R is:

1) -C(=O)CHF ₂ ,

2) -C (= O) CH ₂ NH ₂ ,

3) -C (= O) CH ₂ NHCH ₃ ,

4) -C (= O) CH ₂ NHC (= NH) NH ₂ ,

5) -C(=O)CH ₂ -tetrazolyl or

6) -SO ₂ CH ₃ , or

R and R ⁰ are combined together to give -triazolyl, optionally substituted with -CH ₂ -OH;

and other groups are as represented in the general formula of formula (I), (Ia) or (Ib), above.

In another embodiment, R ⁰ is hydrogen and R is:

-C(=O)CHF ₂ ;

-C(=O)CH ₂ NH ₂ ;

-C(=O)CH ₂ NHCH ₃ ;

-C(=O)CH ₂ NHC(=NH)NH ₂ ;

-C(=O)CH ₂ -tetrazolyl; or

-SO ₂ CH ₃ ; or

R and R ⁰ are combined together to give -triazolyl, optionally substituted with -CH ₂ -OH.

In another embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt thereof, wherein R ¹ is:

1) pyrrolidinyl substituted with 1 or 2 of

a) -CONR ^c R ^d ,

b) -CON(CH ₃ )CH ₂ CH ₂ C(=O)-pyrrolidin-1-yl substituted with NH ₂ or diazepanil,

c) -CH ₂ NR ^f R ^g ,

d) -CH=NH,

e) F

f) -(CH ₂ ) _0-1 NHC(=NH)NH ₂ ,

g) -CH ₂ NHSO ₂ -pyrrolidinyl-NH ₂ ,

h) -CH ₂ NH(C=O)-pyrrolidinyl substituted with NH ₂ or F,

i) -CH ₂ NH(C=O)- pyridinyl substituted with oxo, CH ₃ and OH,

j) -CH ₂ NH(C=O)- cyclopentyl-NH ₂ ,

k) -CH ₂ NHSO ₂ -piperazine,

l) -CH ₃ or

m)OH,

,2)

,

3) -CH ₂ -pyridinyl,

4) thiazole substituted with pyridinyl, where pyridinyl is optionally substituted with -CH ₃ or -CH ₂ C(=O)NH ₂ ,

5) azetidinyl substituted with -C(=NH)NH ₂ ,-SO ₂ NH ₂ , thiazolyl or 4,5-dihydrothiazol-2-yl,

6) -CH ₂ CH ₂ -pyridinyl substituted with oxo, CH ₂ NH ₂ and OH,

7) -CH ₂ -pyrrolidinyl substituted with acetyl and -NH ₂ , or -NHSO ₂ NH ₂ ,

8) -CH ₂ -piperazine,

9) -CH ₂ CH ₂ -NH (= NH) NH ₂ ,

,ten)

,

11) pyrazole optionally quaternized with -CH ₃ and optionally substituted with -CH ₂ pyrrolidine, or CH ₂ piperidine optionally quaternized with -CH ₃ and optionally substituted with -CH ₂ CH ₂ NH ₂ ,

12) -CH ₂ -phenyl substituted with pyrazole, optionally quaternized with -CH ₃ and substituted with -(CH ₂ ) ₃ NH ₂ , or

13) -CH ₂ CH ₂ NHCO ₂ - tert -butyl;

and other groups are as represented in the general formula of formula (I), (Ia) or (Ib) above or in the seventh or eighth embodiments.

In another embodiment, R ¹ is:

1) pyrrolidinyl substituted with 1 or 2 of

-CONR ^c R ^d ;

-CON(CH ₃ )CH ₂ CH ₂ C(=O)-pyrrolidin-1-yl substituted with NH ₂ or diazepanil;

-CH ₂ NR ^f R ^g ;

-CH=NH;

F;

-CH ₂ NHSO ₂ -pyrrolidinyl-NH ₂ ;

-CH ₂ NH(C=O)- pyrrolidinyl substituted with NH ₂ or F;

-CH ₂ NH(C=O)- pyridinyl substituted with oxo, CH ₃ and OH;

-CH ₂ NH(C=O)- cyclopentyl-NH ₂ ;

-CH ₂ NHSO ₂ -piperazine; or

_-CH3 ;

;2)

;

3) -CH ₂ -pyridinyl;

4) a thiazole substituted with pyridinyl, wherein the pyridinyl is optionally substituted with CH ₃ ;

5) azetidinyl substituted with thiazolyl or 4,5-dihydrothiazol-2-yl;

6) -CH ₂ CH ₂ -pyridinyl substituted with oxo, CH ₂ NH ₂ and OH;

7) -CH ₂ -pyrrolidinyl substituted with acetyl and -NH ₂ or -NHSO ₂ NH ₂ ; or

8) -CH ₂ -piperazine.

In a tenth embodiment, the present invention provides a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide or pharmaceutically acceptable salt thereof, wherein R ¹ is pyrrolidinyl substituted with

1) -C(=O)NR ^c R ^d ;

2) -CH ₂ NHSO ₂ NH ₂ , or

3) -CH ₂ -pyrrolidinyl-NH ₂ or

4) -CH ₂ -CO-pyrrolidinyl-NH ₂ ;

where

R ^c is -CH ₃ ,

R ^d is -CH ₃ ;

R ^c and R ^d are taken together with the N to which they are connected, getting

1) azetidinyl, optionally substituted-NHC(=NH)NH ₂ ,

2) pyrrolidinyl, substituted

a. one or two -NH ₂ ,

b. _-NHCH3 ,

c. -C (Me) ₂ NH ₂ ,

d. one or two -OH,

e. -CH ₂ NH ₂ ,

f. -NHC(=O)CH ₂ NH ₂ ,

g. -NHC(=O)CH ₂ CH ₂ NH ₂ ,

h. -NHC(=O)CH ₂ NH(=NH)NH ₂ ,

i. -NHCH=NH,

j. -F and -NH ₂ ,

k. -NH ₂ and -OH,

l. -NH ₂ and -CH ₃ ,

m. -NH ₂ and -CH ₂ OH,

n. -NH ₂ and -CH ₂ NH ₂ ,

o. -NH ₂ and -OMe,

p. -OH and -CH ₂ NH ₂ ,

q. -CH ₂ OH and -CH ₂ NH ₂ ,

r. -NH ₂ and -COOH,

s. -NHC(=NH)NH ₂ ,

t. -NHC(=NH)NH ₂ and -OH,

u. -NHC(=NH)NH ₂ and -CH ₂ OH,

v. -NHC(=NH)NH ₂ and -NH ₂ ,

w. -NH ₂ and -CH ₂ NHSO ₂ NH ₂ ,

x. -CH ₂ F and NH ₂ ,

y. -OH, -NH ₂ and -CH ₂ NH ₂ ,

z. -OH, -NH ₂ and -CH ₂ OH or

a.a. triazolyl substituted with -CH ₂ NH ₂ ,

3) piperidinyl substituted with - (CH ₂ ) _0-2 NH ₂ , -CH ₂ NHCH ₂ C(=O)NH ₂ , -CH ₂ CH ₂ NH ₂ , -CH ₃ and -NH ₂ , -CH ₂ OH and -CH ₂ NH ₂ , -F and -NH ₂ , -OH and -NH ₂ , -CONHCH ₂ CH(OH)CH ₂ NH ₂ or azetidinyl substituted with -OH or piperazinyl,

4) piperazinyl optionally substituted with one or two -CH ₃ , -CH ₂ NH ₂ , -CH ₂ CH ₂ NH ₂ , -C(=NH)NH ₂ , -CH ₂ CH ₂ NHC(=NH)NH ₂ , - C(=O)(CH ₂ ) _1-2 NH ₂ , -C(=O)CH(NH ₂ )NH ₂ , -CH ₂ CH(NH ₂ )CH ₂ NH ₂ , -CH ₂ CH(F)CH ₂ NH ₂ , -C(=O)CH ₂ NHCH ₃ , -C(=O)CH(NH ₂ )CH ₂ OH or -CH ₃ and -CH ₂ C(=O)NH ₂ ;

5) morpholinyl optionally substituted with -CH ₂ NH ₂ ;

6) 1,4-diazepane, optionally substituted with -C(=NH)NH ₂ ;

7) octahydro-1H-pyrrolo[3,2-c]pyridine, optionally substituted with -CH ₂ CH ₂ NH ₂ , -CH ₂ CH(OH)NH ₂ or -C(=NH)NH ₂ ,

8) octahydrocyclopenta[c]pyrrole, optionally substituted

a. one or two -NH ₂ ,

b. -NH ₂ and -CH ₂ OH,

c. -NH ₂ and -CH ₂ NH ₂ ,

d. _-NH2 ,

e. -NHC(=NH)NH ₂ ,

f. -NHC(=NH)NH ₂ and -CH ₂ OH or

g. s-OH, -NH ₂ and -CH ₂ OH,

9) octahydro-1H-pyrrolo[2,3-c]pyridine,

10) octahydro-1H-pyrrolo[3,2-c]pyridine, optionally substituted with -CH ₂ CH(OH)CH ₂ NH ₂ ,

11) octahydro-1H-pyrrolo[3,4-b]pyridine, optionally substituted with -CH ₂ OH,

12) octahydropyrrolo[3,4-b]pyrrole optionally substituted with -CH ₂ OH, -CH ₂ CH ₂ NH ₂ or -C(=NH)NH ₂ ;

13) octahydro-1H-pyrrolo[3,4-c]pyridine optionally substituted with -CH ₂ OH or -COOH;

14) 5,5-dimethyloctahydro-1H-pyrrolo[3,2-c]pyridine-1--5-th,

15) octahydropyrrolo[3,4-c]pyrrole, optionally substituted with -CH ₂ OH,

16) octahydropyrrolo[3,4-d]imidazole, optionally substituted with =NH,

17) octahydro-1H-pyrrolo[3,2-b]pyridine,

18) octahydropyrrolo[3,4-b][1,4]oxazine,

19) 3,6-diazabicyclo[3,2,0]heptane,

20) 1,9-diazaspiro[5,5]undecane,

21) decahydro-1,6-naphthyridine,

22) 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine, optionally substituted-NH ₂ ,

23) 2,7-diazaspiro[4,4]nonane,

24) 2,8-diazaspiro[4,5]decane,

25) 2,6-diazaspiro[3,4]octane,

26) 1,7-diazaspiro[3,5]nonane,

27) 2,7-diazaspiro[3,5]nonane,

28) 1,8-diazaspiro[4,5]decane,

29) 1,7-diazaspiro[4,5]decane,

30) 5-oxa-2-azaspiro[3,4]octane, optionally substituted-NH ₂ ,

31) 3,8-diazatricyclo[5.2.1.01.5]decane or

32) 8-azaspiro[bicyclo[3.2.1]octane-3,3'-pyrrolidine;

and other groups are as represented in the general formula (I), (Ia) or (Ib) above, or in embodiments.

In another embodiment, R ¹ is pyrrolidinyl substituted

-C(=O)NR ^c R ^d ;

-CH ₂ NHSO ₂ NH ₂ ; or

-CH ₂ -pyrrolidinyl-NH ₂ ;

where

R ^c is -CH ₃ ,

R ^d is -CH ₃ ;

R ^c and R ^d are taken together with N to which they are connected to give pyrrolidinyl substituted

one or two -NH ₂ ,

_-NHCH3 ,

two -OH,

-CH ₂ NH ₂ ,

-NHC(=O)CH ₂ NH ₂ ,

-NHCH=NH,

-NH ₂ and -OH,

-NH ₂ and -CH ₃ ,

-NH ₂ and -CH ₂ OH,

-NHC(=NH)NH ₂ and -OH, or

Triazolyl substituted with -CH ₂ NH ₂ ;

Piperidinyl, substituted

-(CH ₂ ) _0-2 NH ₂ ,

-CH ₂ NHCH ₂ C (= O) NH ₂ ,

-CH ₃ and -NH ₂ ,

F and -NH ₂ , or

Azetidinyl substituted with -OH or piperazinil;

Piperazinyl, optionally substituted

one or two -CH ₃ ,

-CH ₂ CH ₂ NH ₂ ,

-C(=NH)NH ₂ ,

-CH ₂ CH ₂ NHC (= NH) NH ₂ ,

-C (= O) (CH ₂ ) _1-2 NH ₂ ,

-C(=O)CH ₂ NHCH ₃ ,

-C(=O)CH(NH ₂ )CH ₂ OH, or

-CH ₃ and -CH ₂ C(=O)NH ₂ ;

octahydro-1H-pyrrolo[3,2-c]pyridine;

1,7-diazaspiro[3,5]nonane;

2,7-diazaspiro[3,5]nonane;

1,8-diazaspiro[4,5]decane; or

8-azaspiro[bicyclo[3,2,1]octane-3,3'-pyrrolidine].

In an eleventh embodiment, the present invention provides a compound of formula (Ia) or a stereoisomer, internal salt, N-oxide or pharmaceutically acceptable salt thereof,

(Ia)

where:

A is NR ⁰ R or -triazolyl substituted with -CH ₂ OH;

R represents:

1) -C(=O)-C _1-6 alkyl-NR ^a R ^b ;

2) -C(=O)CHF ₂ ,

3) -C(=O)CH ₂ SCHF ₂ ,

4) -C (= O) CH ₂ NH (CH ₂ ) ₂ OMe,

5) -C (= O) CH ₂ pyrrolidine,

6) -C (= O) CH ₂ azetidine,

7) -C(=O)CH ₂ piperazine,

8) -C(=O)CH₂pyrrolidine, optional substituted with 1 or 2 substituents selected from fluoro and -CH₂NHMe,

9) -C(=O)CH ₂ -tetrazole optionally substituted with -C(CH ₃ ) ₃ , -CF ₃ , -CHF ₂ , -CH ₃ , -NH ₂ -COOC _1-6 alkyl, thienyl, -CH ₂ NHCH ₃ , -NH ₂ or -COOCH ₂ CH ₃ , or

10) -SO ₂ CH ₃ ;

R ⁰ is H;

R ¹ is

1) Pyrrolidinyl substituted with 1 or 2 -CONR ^c R ^d ,

2) -CH ₂ NHSO ₂ NH ₂ or

3) -CH ₂ -pyrrolidinyl, optionally substituted with -NH ₂ ;

R ^a and R ^b are independently H, -C _1-6 alkyl, -C _3-8 cycloalkyl, -SO ₂ CH ₃ , -CH(=NH), -C(=NH)NH ₂ or -CH ₂ C (=O)NH ₂ ;

R ^c and R ^d are independently H, C _1-3 alkyl, -C(=NH)-pyrrolidinyl, optionally substituted with -NH ₂ , or

R ^c and R ^d are taken together with the N to which they are attached to give a 4-12 membered heterocyclic ring or ring system with 0, 1, 2 or 3 additional heteroaromatic ring atoms selected from N and O; where any ring nitrogen atom of a heterocyclic ring or ring system is optionally quadric-covalent; the ring system is a bridged, fused or spiro ring system; and the 4-12 membered heterocyclic ring or ring system is optionally substituted with 1, 2 or 3 substituents selected from

1) =NH,

2) -C (= O) (CH ₂ ) _1-2 NH ₂ ,

3) -C (= O) CH ₂ NHCH ₃ ,

4) -CH ₂ CH (NH ₂ ) CH ₂ NH ₂ ,

5) -C (= O) CH (NH ₂ ) CH ₂ NH ₂ ,

6) -C (= O) CH (F) CH ₂ NH ₂ ,

7) -C (= O) CH (NH ₂ ) CH ₂ OH,

8) -CH ₂ CH (OH) CH ₂ NH ₂ ,

9) -C (= O) NH CH ₂ CH (OH) CH ₂ NH ₂ ,

10) -C (= NH) NH ₂ ,

11) -COOH,

12) -CH ₃ ,

13) -CH ₂ C (= O) NH ₂ ,

14) -CH ₂ NH CH ₂ C (= O) NH ₂ ,

15) -CH ₂ NR ^h R ^j ,

16) -CH ₂ CH ₂ NH ₂ ,

17) -CH ₂ CH ₂ NH-C (= NH) -NH ₂ ,

18) -CH ₂ NHSO ₂ NH ₂ ,

19) -CH ₂ OH,

20) -C (CH ₃ ) ₂ NH ₂ ,

21) -CH ₂ F,

22) -OH,

23) -OMe,

24) -F,

25) -NR ^h R ^j ,

26) -NHCH=NH,

27) -NH-C (=NH) -NH ₂ ,

28) -NHCOCH ₂ -NH-C (= NH) -NH ₂ ,

29) -NHCOCH ₂ NH ₂ ;

30)-(CH₂)_0-3NR^hR^j, optionally substituted with -NH₂or halogens,

31) Azetidinyl, optionally substituted with -OH,

32) piperazinyl and

33) triazolyl substituted with CH ₂ NH ₂ ; and

R ^h and R ^j are independently H, C _1-6 alkyl or C _3-8 cycloalkyl;

and other groups are as represented in the general formula of formula (I), (Ia) or (Ib) above, or in embodiments.

In another embodiment, the compound has the structure according to formula Ia:

(Ia)

where:

A is NR ⁰ R or -triazolyl substituted with -CH ₂ OH;

R represents:

-C(=O)-C _1-6 alkyl-NR ^a R ^b ;

-C(=O)CHF ₂ ;

-C(=O)CH ₂ -tetrazole optionally substituted with -C(CH ₃ ) ₃ , -CF ₃ , -CHF ₂ , -CH ₃ , -NH ₂ -COOC _1-6 alkyl, thienyl, -CH ₂ NHCH ₃ , -NH ₂ or -COOCH ₂ CH ₃ ; or

-SO ₂ CH ₃ ;

R ⁰ is H;

R ¹ is pyrrolidinyl substituted with 1 or 2 -CONR ^c R ^d ; -CH ₂ NHSO ₂ NH ₂ or -CH ₂ -pyrrolidinyl optionally substituted with -NH ₂ ;

R ^a and R ^b are independently H, -C _1-6 alkyl, -C _3-8 cycloalkyl, -SO ₂ CH ₃ , -CH(=NH), -C(=NH)NH ₂ or -CH ₂ C (=O)NH ₂ ;

R ^c and R ^d are independently C _1-3 alkyl, or

R ^c and R ^d are taken together with the N to which they are connected to give a 4-10 membered heterocyclic ring or ring system with 0, 1 or 2 additional heteroaromatic ring atoms selected from N and O; where any ring nitrogen atom of a heterocyclic ring or ring system is optionally quadric-covalent; the ring system is a bridged, condensed or spiro ring system; and the 4-12 membered heterocyclic ring or ring system is optionally substituted with 1 or 2 substituents selected from

-C (= O) (CH ₂ ) _1-2 NH ₂ ,

-C(=O)CH ₂ NHCH ₃ ,

-C(=O)CH(NH ₂ )CH ₂ OH,

-C(=NH)NH ₂ ,

_-CH3 ,

-CH ₂ C (= O) NH ₂ ,

-CH ₂ NH CH ₂ C (= O) NH ₂ ,

-CH ₂ NR ^h R ^j ,

-CH ₂ CH ₂ NH ₂ ,

-CH ₂ CH ₂ NH-C (= NH) -NH ₂ ,

_-CH2OH ,

-OH,

-F,

-NR ^h R ^j ,

-NHCH=NH,

-NH-C(=NH)-NH ₂ ,

-NHCOCH ₂ NH ₂ ;

-(CH₂)_0-3NR^hR^j, optionally substituted with -NH₂or halogens;

Azetidinyl, optionally substituted with -OH,

piperazinil and

Triazolyl substituted with CH ₂ NH ₂ ; and

R ^h and R ^j are independently H, C _1-6 alkyl or C _3-8 cycloalkyl.

In another embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or its stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt,

where

R ⁰ is hydrogen or C _1-6 alkyl which is optionally substituted with one or two substituents selected from halo, hydroxyl, cyano, carbamoyl, -SO ₂ NH ₂ and C _1-6 alkoxy;

R represents:

1) -(CH ₂ ) _n C(=O)R ² ,

2) -(CH ₂ ) _n C(=S)R ² ,

3) -(CH ₂ ) _n SO ₂ R ² ,

4) -C _1-6 alkyl optionally substituted with -C _3-6 cycloalkyl, or

5) -CH(=NH), or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3, or 4 additional heteroaromatic ring atoms independently selected from N, O, and S, provided that when R and R ⁰ , together with the N to which they are attached, form a triazole, then Z is not H.

In another embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or its stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt,

where

R ⁰ is hydrogen or C _1-6 alkyl which is optionally substituted with one or two substituents selected from halo, hydroxyl, cyano, carbamoyl, -SO ₂ NH ₂ and C _1-6 alkoxy;

R represents:

1) -(CH ₂ ) _n C(=O)R ² ,

2) -(CH ₂ ) _n C(=S)R ² ,

3) -(CH ₂ ) _n SO ₂ R ² ,

4) -C _1-6 alkyl optionally substituted with -C _3-6 cycloalkyl, or

5) -CH(=NH), or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3, or 4 additional heteroaromatic ring atoms independently selected from N, O, and S, provided that when R and R ⁰ , together with the N to which they are attached, form a triazole or tetrazole, then Z is not H.

In another embodiment, the present invention provides a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt thereof, wherein

R is -(CH ₂ ) _n C(=O)R ² , -(CH ₂ ) _n C(=S)R ² , -(CH ₂ ) _n SO ₂ R ² , or -CH(=NH); or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S;

provided that

when R is -(CH ₂ ) _n C(=O)R ² , n is 0, and R ⁰ is H, then R ² is not unsubstituted C _1-6 alkyl;

when R is -(CH ₂ ) _n C(=O)R ² and n is not 0, R ² is not OH or NH ₂ ;

when R is -(CH ₂ ) _n SO ₂ R ² and n is not 0, R ² is not OH or NH ₂ ; and

when R and R ^o are combined together to form a triazole, Z is not H.

In another embodiment, the present invention provides a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt thereof, wherein

R is -(CH ₂ ) _n C(=O)R ² , -(CH ₂ ) _n C(=S)R ² , -(CH ₂ ) _n SO ₂ R ² , or -CH(=NH); or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S;

provided that

when R is -(CH ₂ ) _n C(=O)R ² , n is 0, and R ⁰ is H, then R ² is not substituted with C _1-6 alkyl;

when R is -(CH ₂ ) _n C(=O)R ² and n is not 0, R ² is not OH or NH ₂ ;

when R is -(CH ₂ ) _n SO ₂ R ² and n is not 0, R ² is not OH or NH ₂ ; and

when R and R ^o are combined together to give a triazole or tetrazole, then Z is not H.

In another embodiment, the present invention provides a compound of formula (I), (Ia) or (Ib), or a stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt thereof, wherein

R is -(CH ₂ ) _n C(=O)R ² , -(CH ₂ ) _n C(=S)R ² , -(CH ₂ ) _n SO ₂ R ² , or -CH(=NH); or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S;

provided that

when R is -(CH ₂ ) _n C(=O)R ² , n is 0 and R ⁰ is H, then R ² is not unsubstituted C _1-6 alkyl; and/or

when R is -(CH ₂ ) _n C(=O)R ² and n is not 0, R ² is not OH or NH ₂ ; and/or

when R is -(CH ₂ ) _n SO ₂ R ² and n is not 0, R ² is not OH or NH ₂ ; and/or

when R and R ^o are combined together to give a triazole or tetrazole, then Z is not H.

In another embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or its stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt,

where R is -(CH ₂ ) _n C(=O)R ² , -(CH ₂ ) _n C(=S)R ² , -(CH ₂ ) _n SO ₂ R ² , or -CH(=NH) ; or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S;

provided that

when R is -(CH ₂ ) _n C(=O)R ² , n is 0, and R ⁰ is H, then R ² is not unsubstituted C _1-6 alkyl;

when R is -(CH ₂ ) _n C(=O)R ² and n is not 0, R ² is not OH or NH ₂ ;

when R is -(CH ₂ ) _n SO ₂ R ² and n is not 0, R ² is not OH; and

when R and R ^o are combined together to give a triazole or tetrazole, then Z is not H.

In another embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or its stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt,

where R is -(CH ₂ ) _n C(=O)R ² , -(CH ₂ ) _n C(=S)R ² , -(CH ₂ ) _n SO ₂ R ² , or -CH(=NH) ; or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S;

provided that

when R is -(CH ₂ ) _n C(=O)R ² , n is 0, and R ⁰ is H, then R ² is not unsubstituted C _1-6 alkyl;

when R is -(CH ₂ ) _n C(=O)R ² and n is not 0, R ² is not OH or NH ₂ ;

when R is -(CH ₂ ) _n SO ₂ R ² and n is 0, R ⁰ is not H;

when R is -(CH ₂ ) _n SO ₂ R ² and n is not 0, R ² is not OH; and

when R and R ^o are combined together to form a triazole, Z is not H.

In another embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or its stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt,

where R is -(CH ₂ ) _n C(=O)R ² , -(CH ₂ ) _n C(=S)R ² , -(CH ₂ ) _n SO ₂ R ² , or -CH(=NH) ; or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S;

provided that

when R is -(CH ₂ ) _n C(=O)R ² , n is 0 and R ⁰ is H, then R ² is not unsubstituted C _1-6 alkyl;

when R is -(CH ₂ ) _n C(=O)R ² and n is not 0, R ² is not OH or NH ₂ ;

when R is -(CH ₂ ) _n SO ₂ R ² and n is 0, R ⁰ is not H;

when R is -(CH ₂ ) _n SO ₂ R ² and n is not 0, R ² is not OH; and

when R and R ^o are combined together to give a triazole or tetrazole, then Z is not H.

In another embodiment, the present invention relates to a compound of formula (I), (Ia) or (Ib), or its stereoisomer, internal salt, N-oxide, or pharmaceutically acceptable salt,

where

R is -(CH ₂ ) _n C(=O)R ² , -(CH ₂ ) _n C(=S)R ² , -(CH ₂ ) _n SO ₂ R ² , or -CH(=NH); or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S;

provided that

when R is -(CH ₂ ) _n C(=O)R ² , n is 0, and R ⁰ is H, then R ² is not unsubstituted C _1-6 alkyl;

when R is -(CH ₂ ) _n C(=O)R ² and n is not 0, R ² is not OH or NH ₂ ;

when R is -(CH ₂ ) _n SO ₂ R ² and n is 0, R ⁰ is not H; and

when R is -(CH ₂ ) _n SO ₂ R ² and n is not 0, R ² is not OH.

In another embodiment of the present invention,

R is -(CH ₂ ) _n C(=O)R ² , -(CH ₂ ) _n C(=S)R ² , -(CH ₂ ) _n SO ₂ R ² , or -CH(=NH); or

R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from N, O and S;

provided that

when R is -(CH ₂ ) _n C(=O)R ² and n is 0, R ⁰ is not H;

when R is -(CH ₂ ) _n C(=O)R ² and n is not 0, R ² is not OH or NH ₂ ;

when R is -(CH ₂ ) _n SO ₂ R ² and n is 0, R ⁰ is not H; and

when R is -(CH ₂ ) _n SO ₂ R ² and n is not 0, R ² is not OH.

In another embodiment of the present invention, R ¹ is C _2-6 aminoalkyl, optionally substituted with -CR ^x =NR ^x .

In another embodiment, A is -NR ⁰ R. In another embodiment, A is -OR ^z .

In another embodiment, Z is -H. In another embodiment, Z is -CH ₃ .

In another embodiment, X is -S-. In another embodiment, X is -CH ₂ -.

In another embodiment, R ⁰ is hydrogen.

In another embodiment, R is -(CH ₂ ) _n C(=O)R ² .

In another embodiment, R ¹ is -(CH ₂ ) _0-6 -HetC or -(CH ₂ ) _1-6 NH(C=NH)NH ₂ . In another embodiment, R ¹ is HetC or -(CH ₂ ) _2- NH(C=NH)NH ₂ .

In another embodiment, R ¹ is -(CH ₂ ) _0-6 -HetC. In another embodiment, R ¹ is -HetC.

In another embodiment, R ¹ is -(CH ₂ ) _1-6 NH(C=NH)NH ₂ . In another embodiment, R ¹ is -(CH ₂ ) ₂ -NH(C=NH)NH ₂ .

In another embodiment, R ² is AryA. In another embodiment, R ² is a tetrazole.

In another embodiment, R ⁴ is -CO ₂ H.

In one embodiment, HetC is a substituted or unsubstituted pyrrolidine.

In one embodiment, R ^c is -C(=NH)-pyrrolidin-1-yl substituted with NH ₂ .

In another embodiment, R ^d is hydrogen.

In another embodiment, R ^c and R ^d are taken together with the N to which they are attached to give a heterocyclic ring or ring system selected from: azetidine, pyrrolidine, piperazine, octahydropyrrolo[3,4-b]pyrrole, octahydro-1H- pyrrolo[3,2-c]pyridine, 2,7-diazaspiro[4,4]-nonane, octahydropyrrolo[3,4-d]imidazole and 3,8-diaza-tricyclo[5,2,1,01,5 ]decane, where the heterocyclic ring or ring system is optionally substituted with 1, 2, 3 or 4 substituents independently selected from: =NH, -(CH ₂ ) _0-3 OH, -CH ₂ CH(OH)CH ₂ NH ₂ , - (CH ₂ ) _0-3 NR ^h R ^j , optionally substituted-NH ₂ , -NHC(=O)CH ₂ NHC(=NH)NH ₂ , -C(=NH)NH ₂ and -(CH ₂ ) _{0- 3} NHC(=NH)NH ₂ .

In another embodiment, R ^c and R ^d are taken together with the N to which they are attached to give a heterocyclic ring or ring system selected from: azetidine, pyrrolidine, piperazine, octahydropyrrolo[3,4-b]pyrrole, octahydro-1H- pyrrolo[3,2-c]pyridine, 2,7-diazaspiro[4,4]nonane, octahydropyrrolo[3,4-d]imidazole and 3,8-diaza-tricyclo[5,2,1,01,5] decane, where the heterocyclic ring or ring system is optionally substituted with 1, 2, 3 or 4 substituents independently selected from: =NH, -CH ₂ OH, OH, -CH ₂ CH(OH)CH ₂ NH ₂ , -(CH ₂ ) ₃ NH ₂ , optionally substituted-NH ₂ , -CH ₂ CH(NH ₂ )CH ₂ NH ₂ , -NHC(=O)CH ₂ NHC(=NH)NH ₂ , -C(=NH)NH ₂ , and - NHC(=NH)NH ₂ .

In another embodiment. each R ^x and R ^y is independently hydrogen.

In another embodiment, HetC is substituted with one substituent selected from -C(=O)NR ^c R ^d .

In another embodiment of the present invention, the pharmaceutically acceptable salt is selected from sodium, potassium, calcium, magnesium and ammonium salts. In the twelfth embodiment of the present invention, the compound of the present invention is selected from the exemplary embodiments shown in Examples 1-601 below and their pharmaceutically acceptable salts.

In the thirteenth embodiment of the present invention, the compound of the present invention is selected from the exemplary embodiments shown in examples 32, 44, 95, 103, 106, 112, 120, 121, 124, 129, 132, 135, 146, 149, 157, 158, 159, 161, 168, 169, 176, 178, 184, 186, 218, 219, 221, 242.264, 278, 283, 298, 314, 324, 352, 360, 361, 362, 363, 364, 365 367 368 391 395 396 397 398 400 404 411 412 413 414 419 420 425 426 427 429 431 432 433 435 437 438 439. 457, 481, 493, 505, 521, 523, 544, 545, 560, 566, 567, 571, 575, 576, 580, 584, 585, 593 below, and their pharmaceutically acceptable salts.

References to various embodiments regarding compounds of formula I or (I) in particular include various embodiments of formula I such as formulas Ia and Ib, sub-embodiments of formulas Ia and Ib, other embodiments present in the present invention, and individual compounds described in the present invention.

Other embodiments of the present invention include the following:

(a) A pharmaceutical composition containing a compound of formula I or Ia or Ib as defined in the present invention, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

(b) Pharmaceutical composition (a) further comprising a beta-lactamase inhibitor.

(c) Pharmaceutical composition (b), wherein the beta-lactamase inhibitor is clinically approved clavulanic acid and its salts, sulbactam and its salts, tazobactam and its salts, avibactam and its salts, and cilastatin and its salts. Other beta-lactamase inhibitors include relebactam, RPX 7009 and BAL 30072.

(d) A pharmaceutical composition which contains (i) a compound of formula (I), (Ia) or (Ib), or a pharmaceutically acceptable salt thereof, and (ii) a beta-lactamase inhibitor, wherein each of the compound of formula I or Ia or Ib , and a beta-lactamase inhibitor are used in an amount that makes the combination effective in overcoming drug resistance in bacterial infection.

(e) Combination (d), wherein the beta-lactamase inhibitor is clinically approved clavulanic acid and its salt, sulbatcam and its salt, tazobactam and its salt, avibactam and its salt, and cilastatin and its salt. Other beta-lactamase inhibitors include relebactam, RPX 7009 and BAL 30072

(f) A method of inhibiting the synthesis of bacterial peptidoglycans, which comprises administering to a subject in need of treatment an effective amount of a compound of formula I or Ia or Ib, or a pharmaceutically acceptable salt thereof.

(g) A method of preventing and/or treating a bacterial infection, which comprises administering to a subject in need of treatment an effective amount of a compound of Formula I or Ia or Ib, or a pharmaceutically acceptable salt thereof.

(h) A method of treating a bacterial infection, which comprises administering to a subject in need of treatment a therapeutically effective amount of composition (a), (b), (c), (d) or (e).

(i) A method of treating a bacterial infection as set forth in (f), (g), or (h), wherein the bacterial infection is the result of Escherichia spp. or Pseudomonas spp. , Staphylococcus spp . or Streptococcus spp.

The present invention also includes a compound of formula I or Ia or Ib, or a pharmaceutically acceptable salt thereof,

(1) for application in,

(2) for use as a medicinal product for or

(3) for use in the preparation (or manufacture) of a medicinal product for medicine or inhibition of the synthesis of bacterial peptidoglycans or treatment of a bacterial infection. In these uses, the compounds of the present invention may optionally be used in combination with one or more beta-lactamase inhibitors.

Additional embodiments of the present invention include the pharmaceutical compositions, combinations and methods referred to in (a)-(i) above and the uses referred to in the previous paragraph, where the compound of the present invention used in the present invention is a compound of one of the embodiments, sub-embodiments , classes or subclasses described above. The compound may optionally be used as a pharmaceutically acceptable salt in these embodiments.

In the embodiments of the compounds and salts presented above, it is clear that each embodiment can be combined with one or more other embodiments such that the combination produces a stable compound or salt and is as described in the embodiments. In addition, it is clear that the embodiments of the compositions and methods presented in (a)-(i) above include all embodiments of the compounds and/or salts, including such embodiments as a result of combinations of embodiments.

Additional embodiments of the present invention include each of the pharmaceutical compositions, combinations, methods and uses set forth in the preceding paragraphs, where

Used in the present invention, the compound of the present invention or its salt is essentially pure. With regard to a pharmaceutical composition containing a compound of formula I or a salt thereof and a pharmaceutically acceptable carrier and optionally one or more excipients, it is clear that the term "substantially pure" refers to a compound of formula I or a salt thereof by itself; i.e., the purity of the active ingredient in the composition.

Definitions:

"Alkyl" denotes saturated carbon chains, which may be straight or branched, or combinations thereof, unless the carbon chain is otherwise defined. Other groups having the prefix "alk", such as alkoxy and alkanoyl, may also be linear or branched, or combinations thereof, unless the carbon chain is otherwise specified. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, sec- and tert -butyl, pentyl, hexyl, heptyl, octyl, and the like.

"Alkenyl" refers to carbon chains that contain at least one carbon-carbon double bond, and which may be linear or branched, or combinations thereof, unless otherwise specified. Examples of alkenyl include vinyl, allyl, isopropenyl, pentenyl, hexenyl, heptenyl, 1-propenyl, 2-butenyl, 2-methyl-2-butenyl and the like.

An "antibiotic" refers to a compound or composition that reduces the viability of a microorganism, or that inhibits the growth or proliferation of a microorganism. The phrase "inhibits growth or proliferation" means an increase in generation time (ie, the period of time required for a bacterial cell to divide or a population to double) by at least about 2-fold. Preferred antibiotics are antibiotics that can increase the generation time by at least about 10-fold or more (eg, at least about 100-fold or even indefinitely, as in the case of complete cell death). As used in the present description, it is assumed that the antibiotic further includes an antimicrobial, bacteriostatic or bactericidal agent.

"Approximately", when modifying the amount (e.g., kg, l, or equivalents) of the substrate or composition, or the value of a physical property, or the value of a parameter indicative of a process step (e.g., the temperature at which the process step is carried out) or the like, refers to a change in the numerical value, which may occur, for example, in standard methods of measurement, processing and sampling used in the preparation, characterization and/or use of a substance or composition; due to random error in these methods; due to differences in the manufacturer, source or purity of the ingredients used to prepare or use the compositions or the implementation of the methods; and the like. In certain embodiments, "about" may be a change of ±0.1, 0.2, 0.3, 0.4, 0.5, 1.0, 2.0, 3.0, 4.0, or 5.0 suitable unit. In certain embodiments, "about" may represent a change of ±1%, 2%, 3%, 4%, 5%, 10%, or 20%.

"Aromatic ring system", according to the examples in the present invention, AryA, AryB and AryC, means a monocyclic, bicyclic or tricyclic aromatic ring or a ring system containing 5-14 ring atoms, where at least one of the rings is aromatic. Aromatic ring systems as used in the present invention include aryls and heteroaryls. The term may be used to describe a carbocyclic ring fused to an aryl group. For example, a 5-7 membered cycloalkyl may be fused through two adjacent ring atoms with a 5-6 membered heteroaryl containing 1, 2, or 3 heteroaromatic ring atoms selected from N, O, and S. In another example, a heteromonocyclic ring is fused through two ring atoms with a phenyl or a 5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, and S.

"Aryl" means a monocyclic, bicyclic or tricyclic carbocyclic aromatic ring or a ring system containing 6-14 carbon atoms, where at least one of the rings is aromatic. Examples of aryl include phenyl and naphthyl.

"Cycloalkyl" means a saturated monocyclic, bicyclic or bridged carbocyclic ring containing the number of carbon atoms indicated. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.

"Drug resistance" refers to a bacterium that is no longer susceptible to at least one previously effective drug; which has developed the ability to tolerate antibiotic attack from at least one previously effective drug. A drug-resistant strain can pass on this ability of resistance to its offspring. Said resistance may be the result of random genetic mutations in a bacterial cell that alter its sensitivity to one drug or to different drugs.

"Halogen" includes fluorine, chlorine and bromine.

"Heteroaryl" means a monocyclic, bicyclic or tricyclic ring or ring system containing 5-14 carbon atoms and containing at least one ring heteroatom selected from N, NH, N as a quaternary salt, S (including SO and SO ₂ ) and O, where at least one of the rings containing the heteroatom is aromatic. Examples of heteroaryl include pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, pyridyl, oxazolyl, oxadiazolyl, thiadiazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl, triazinyl, thienyl, pyrimidyl, pyridazinyl, pyrazinyl, benzisoxazolyl, benzoxazolyl, benzothiazolyl, benzothiazolyl, benzimidazolyl , benzothienyl (including S-oxide and dioxide), benzotriazolyl, furo(2,3-b)pyridyl, quinolyl, indolyl, isoquinolyl, quinazolinyl, dibenzofuranyl, and the like.

"Heterocycle" means a monocyclic, bicyclic or tricyclic saturated or monounsaturated ring or ring system containing 3-14 carbon atoms and containing at least one ring heteroatom selected from N, NH, N as a quaternary salt, S (including SO and SO ₂ ) and O. When the heterocycle contains two rings, the rings may be fused, bridged, or spiro-linked. Examples of monocyclic heterocyclic rings include piperazine, piperidine and morpholine. When the heterocycle contains two or more rings, the rings may be fused, bridged, and/or spiro-linked. Examples of monocyclic heterocyclic rings include piperazine, piperidine and morpholine. Examples of tricyclic ring systems include 8-azaspiro[bicyclo[3.2.1]octane-3,3'-pyrrolidine.

"Oxo" denotes an oxygen atom connected to another atom by a double bond, and it can be represented by "=O".

Another embodiment of the present invention is a compound of Formula I, or a pharmaceutically acceptable salt thereof, as originally defined or as defined in any of the preceding embodiments, sub-embodiments, aspects, classes, or sub-classes, wherein the compound or salt thereof is in substantially pure form. As used herein, "substantially pure" means suitably at least about 60% by weight, typically at least about 70% by weight, preferably at least about 80% by weight, more preferably at least at least about 90% by weight (for example, from about 90% by weight to about 99% by weight), even more preferably at least about 95% by weight (for example, from about 95% by weight to about 99% by weight, or from about 98% by weight to 100% by weight), and most preferably at least about 99% by weight (for example, 100% by weight) of the product containing the compound of formula I or its salt (for example, product isolated from the reaction mixture to give a compound or salt). The purity of compounds and salts can be determined using standard analysis methods such as thin layer chromatography, gel electrophoresis, high performance liquid chromatography and/or mass spectrometry. If more than one method of analysis is used, and the methods give experimentally significant differences in a certain degree of purity, then the method that provides the highest degree of purity is decisive. A 100% pure compound or salt is a compound or salt that contains no detectable impurities, as determined by a standard assay method.

The listing or depiction of a specific compound in a claim (i.e. species) without a specific stereoconfiguration designation, or with this designation for less than all chiral centers, is intended to include the racemate, racemic mixtures, each individual enantiomer, diastereomeric mixture, and each individual diastereomer of the compound, when these shapes are made possible by the presence of one or more asymmetric centers.

With regard to the compound of the present invention, which contains one or more asymmetric centers and may be in the form of mixtures of stereoisomers, an essentially pure compound may be either an essentially pure mixture of stereoisomers or an essentially pure individual diastereomer or enantiomer. All isomeric forms of these compounds, singly or as mixtures, are included within the scope of the present invention.

When any variable (eg, R ¹ , R ^a , etc.) occurs more than once in any constituent or formula I, its definition at each occurrence is independent of its definition at every other occurrence. Furthermore, combinations of substituents and/or variables are only possible if these combinations result in stable compounds. The wavy line across the bond in the substituent variable represents the point of attachment.

In accordance with the standard nomenclature used throughout this description, the end part of the specified side chain is described last, with the preceding adjacent functional group towards the point of attachment.

In selecting the compounds of the present invention, one skilled in the art will appreciate that the various substituents, i. R ¹ , R ² etc., should be selected in accordance with well known principles of connection and stability of the chemical structure.

The term "substituted" is intended to include multiple degrees of substitution with the named substituent. When multiple substitution moieties are described or claimed, the substituted compound may be independently substituted with one or more of the substitution moieties described or claimed, singly or multiple. By independently substituted is meant that the (two or more) substituents may be the same or different.

When a group, such as C _1-8 alkyl, is indicated as substituted, these substitutions may also occur when that group is part of a larger substituent, such as -C _1-8 alkyl-C _3-7 cycloalkyl and -C _1-8 alkylaryl .

In compounds of formula I, the atoms may have their natural isotopic distribution, or one or more of the atoms may be artificially enriched in a particular isotope having the same atomic number but an atomic mass or mass number different from the atomic mass or mass number predominantly found in nature. The present invention is intended to include all suitable isotopic variants of the compounds of formula I. For example, various isotopic forms of hydrogen (H) include protium ( ¹ H) and deuterium ( ² H or D). Protium is the predominant hydrogen isotope found in nature. Enrichment with deuterium may provide certain therapeutic benefits, such as increased in vivo half-life or reduced dosage requirements, or may provide a compound useful as a standard for characterizing biological samples. The isotopically enriched compounds in formula I can be prepared without undue experimentation by conventional methods well known to those skilled in the art, or by methods analogous to those described in the examples herein, using suitable isotopically enriched reagents and/or intermediates.

Unless explicitly stated otherwise in a particular context, any of the various cyclic rings and ring systems described in the present invention may be attached to the remainder of the compound at any ring atom (i.e., any carbon atom or any heteroatom), provided that it is obtained in the result is a stable connection.

Unless explicitly stated otherwise, all ranges given in the present invention are inclusive. For example, a heteroaromatic ring described as containing "1-4 heteroatoms" means that the ring may contain 1, 2, 3, or 4 heteroatoms. It is also clear that any range given in the present invention includes within its scope all of the subranges within this range. Thus, for example, a heterocyclic ring described as containing "1-4 heteroatoms" is intended to include, as its aspects, heterocyclic rings containing 2-4 heteroatoms, 3 or 4 heteroatoms, 1-3 heteroatoms, 2 or 3 heteroatoms, 1 or 2 heteroatoms, 1 heteroatom, 2 heteroatoms, 3 heteroatoms and 4 heteroatoms. Similarly, C _1-6 when used with a chain, for example an alkyl chain, means that the chain may contain 1, 2, 3, 4, 5, or 6 carbon atoms. It also includes all ranges included in it, including C _1-5 , C _1-4 , C _1-3 , C _1-2 , C _2-6 , C _3-6 , C _4-6 , C _5-6 and all other possible combinations.

A "stable" compound is one that can be prepared and isolated and whose structure and properties remain unchanged, or can be made to remain unchanged for a period of time sufficient to allow the compound to be used for the purposes described in the present invention (e.g., therapeutic introduction to the subject). The compounds of the present invention are limited to the stable compounds included in formula I.

The term "compound" refers to the free compound and, to the extent that they are stable, any hydrate or solvate thereof. A hydrate is a compound complexed with water, and a solvate is a compound complexed with an organic solvent.

As indicated above, the compounds of the present invention can be used in the form of pharmaceutically acceptable salts. The term "pharmaceutically acceptable salt" refers to a salt that has the efficacy of the parent compound and that is not biologically or otherwise undesirable (eg, toxic or otherwise harmful to its recipient). A pharmaceutically acceptable salt can be obtained, for example, by treating a compound of the present invention (eg, a compound of formula I) with one molar equivalent of a weak base (eg, sodium carbonate, sodium bicarbonate, potassium bicarbonate, or sodium acetate). In this case, M is a cation, such as Na ⁺ in the case of treatment with sodium base.

Also described in the present invention are prodrugs of the compound of the present invention which, when administered, undergo chemical transformation by metabolic processes before becoming active pharmacological agents. In general, these prodrugs will be functional derivatives of the compound of the present invention which can be readily converted in vivo to a compound of formula (I).

As above, the present invention includes pharmaceutical compositions containing a compound of formula I of the present invention, optionally one or more other active ingredients, and a pharmaceutically acceptable carrier. The characteristics of the carrier will depend on the route of administration. By "pharmaceutically acceptable" is meant that the ingredients of the pharmaceutical composition must be compatible with each other, not interfere with the activity of the active ingredient(s), and not be harmful (eg, toxic) to their recipient. Thus, the compositions of the present invention may, in addition to the inhibitor, contain diluents, excipients, salts, buffers, stabilizers, solubilizers, and other materials well known in the art.

As also described above, the present invention includes a method of treating a bacterial infection which comprises administering to a subject in need of treatment a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof. The term "subject" (or alternatively "patient"), as used in the present invention, refers to an animal, preferably a mammal, most preferably a human, who is the object of treatment, observation or experiment. The term "administering" and variations thereof (eg, "administering" a compound) with reference to a compound of formula I means providing the compound or a pharmaceutically acceptable salt thereof to an individual in need of treatment. When a compound or salt thereof is provided in combination with one or more other active agents, each of "administration" and variations thereof should be understood to include providing the compound or salt thereof and other agents simultaneously or at different times. When the combination agents are administered simultaneously, they may be administered together in the same composition, or they may be administered separately. It is clear that the "combination" of active agents may be a single composition containing all of the active agents, or multiple compositions, each containing one or more of the active agents. In the case of two active agents, the combination may be either a single composition containing both agents, or two separate compositions, each containing one of the agents; in the case of three active agents, the combination may be either a single composition containing all three agents, three different compositions, each containing one of the agents, or two compositions, one containing two agents and the other containing a third agent; and so on.

The compositions and combinations of the present invention are suitably administered in effective amounts. The term "effective amount" as used herein in relation to a nargenicin compound means an amount of the active compound sufficient to inhibit DnaE and/or cause a bactericidal or bacteriostatic effect. In one embodiment, an effective amount is a "therapeutically effective amount" denoting an amount of active compound that can overcome bacterial drug resistance and that is sufficient to inhibit bacterial replication and/or result in bacterial death. When the active compound (ie active ingredient) is administered as a salt, reference to the amount of active ingredient refers to the free acid or free base of the compound.

Administration of a composition of the present invention is suitably parenteral, oral, sublingual, transdermal, topical, intranasal, intratracheal, intraocular, or intrarectal, wherein the composition is suitably formulated for administration by the chosen route using formulation methods well known in the art, including, for example, methods for preparing and administering formulations are described in chapters 39, 41, 42, 44, and 45 of Remington-The Science and Practice of Pharmacy, ^21st edition, 2006. In one embodiment, the compounds of the present invention are administered intravenously in a hospital setting. In another embodiment, the administration is oral in the form of a tablet or capsule or the like. The dosage of the compounds of the present invention and their pharmaceutically acceptable salts may vary within wide limits and must necessarily be adapted, in each particular case, to individual conditions and the pathogen being controlled. In general, for use in the treatment of bacterial infections, the daily dose may be 0.005 mg/kg to 100 mg/kg, 0.01 mg/kg to 10 mg/kg, 0.05 mg/kg to 5 mg/kg , from 0.05 mg/kg to 1 mg/kg. For oral administration, the compositions are preferably provided as tablets containing 1.0-1000 mg of the active ingredient, in particular 1.0, 5.0, 10.0, 15.0. 20.0, 25.0, 50.0, 75.0, 100.0, 150.0, 200.0, 250.0, 300.0, 400.0, 500.0, 600.0, 750, 0, 800.0, 900.0 and 1000.0 mg of the active ingredient for symptomatic dose adjustment for the patient being treated. The compounds can be administered on a schedule of 1-4 times a day, preferably once or twice a day.

In some embodiments, the compound of the present invention is provided as a pharmaceutical formulation for oral, intravenous, intramuscular, nasal, or topical administration. Thus, in some embodiments, the formulation may be formulated into dosage forms such as, but not limited to, a tablet, capsule, liquid (solution or suspension), suppository, ointment, cream, or aerosol. In some embodiments, the described subject matter provides these compounds and/or formulations that are lyophilized and that can be dissolved to form pharmaceutically acceptable formulations for administration, for example, by intravenous or intramuscular injection.

Intravenous administration of a compound of the present invention can be accomplished by dissolving the powdered form of the compound with a suitable solvent. Suitable solvents include, for example, saline solutions (for example, injection of 0.9% sodium chloride) and sterile water (for example, sterile water for injection, bacteriostatic water for injection with methyl paraben and propyl paraben, or bacteriostatic water for injection with 0.9% benzyl alcohol). The powdered form of the compound can be prepared by gamma irradiation of the compound or lyophilization of a solution of the compound, after which the powder can be stored (eg, in a sealed tube) at or below room temperature until dissolved. The concentration of the compound in solution with the dissolved compound for intravenous administration may be, for example, in the range of from about 0.1 mg/mL to about 20 mg/mL.

The methods of the described subject of administration are useful in the treatment of diseases for which they inhibit the occurrence, growth, or spread of a disease, cause regression of a disease, treat a disease, or otherwise improve the general well-being of a subject suffering from or at risk of developing a disease. Thus, according to the described subject matter, the terms "treat", "treatment", and their grammatical variants, as well as the phrase "method of treatment", are intended to include any desired therapeutic intervention, including, but not limited to, a method of treating an existing infection in a subject, and a method of prevention (i.e. ., prevention) of infection, such as in a subject who is undergoing exposure to microbes, as described in the present invention, or who is awaiting exposure to microbes, as described in the present invention.

Infections that can be treated with the compounds of the present invention can be caused by a variety of microbes, including fungi, algae, protozoa, bacteria, and viruses. In some embodiments, the infection is a bacterial infection. Examples of a bacterial infection that may be treated by the methods of the present invention include, but are not limited to, infections caused by one or more of Staphylococcus aureaus, Enterococcus faecalis, Bacillus anthracis , Streptococcus species (e.g., Streptococcus pyogenes and Streptococcus pneumoniae ), Escherichia coli, Pseudomonas aeruginosa , Burkholderia cepacia , Proteus species (e.g. Proteus mirabilis and Proteus vulgaris ), Klebsiella pneumoniae, Acinetobacter baumannii and Strenotrophomonas maltophillia .

In certain embodiments, the infection is an infection with a bacterium selected from Pseudomonas spp., Klebsiella spp ., Enterobacter spp., Escherichia spp., Morganella spp., Citrobacter spp., Serratia spp. or Acintetobacter spp .

In some embodiments, the compound of formula (I), (Ia) or (Ib) is administered prophylactically to prevent or reduce the occurrence of one of: (a) a bacterial infection in a subject at risk of infection; (b) recurrence of the bacterial infection; and (c) combinations thereof. In some embodiments, the compound of formula (I), (Ia) or (Ib) is administered to treat an existing bacterial infection. In some embodiments, a compound of formula ((I), (Ia), or (Ib) is administered to treat an infection with a multidrug-resistant strain (i.e., a strain that is resistant to two or more previously known antibacterial drugs, such as i) carbapenemase-producing enterobacteria that are resistant to cephalosporins and some carbapenems ii) extended-spectrum β-lactamase (ESBL)-producing enterobacteria that are resistant to cephalosporins and penicillins; iii) enterobacteria resistant to aminoglycosides and fluoroquinolone; iv) P. aeruginosa , which synthesizes extended spectrum β-lactamase (ESBL), and v) P. aeruginosa , which is resistant to aminoglycosides and fluoroquinolone. In some embodiments, the compound of formula (I), (Ia) or (Ib) has a minimum inhibitory concentration (MIC) against one or more bacterial species of 25 μg/ml or less. In some embodiments, a compound of formula (I), (Ia) or (Ib) is administered to treat an infection of a multidrug resistant strain.

In some embodiments, the compound of formula I, Ia, has a minimum inhibitory concentration (MIC) against one or more bacterial species of 25 μg/ml or less. MICs can be determined by methods known in the art, for example, as described in Hurdle et al ., 2008, J. Antimicrob. Chemother. 62:1037-1045.

In some embodiments, the methods of the present invention further comprise administering to the subject an additional therapeutic compound. In some embodiments, a compound of the present invention is administered to a subject before, after, or simultaneously as one or more additional therapeutic compounds. In some embodiments, the additional therapeutic compound is an antibiotic.

Thus, the present invention relates in the following aspect to a combination containing a compound of formula I, or a pharmaceutically acceptable salt thereof, together with one or more additional therapeutic agents. Examples of this one or more additional therapeutic agents include, but are not limited to, β-lactams, aminoglycosides, tetracyclines, macrocycles, oxazolidinones, glycopeptides, lipopeptides, quinolones, etc.

Thus, other antibiotics that can be combined with compounds of formula I or Ia or Ib are, for example, vancomycin, linezolid, tedizolid, ceftaroline, ceftobiprol, ceftalosan, daptomycin, dalbavacin, telavancin, oritavancin, aztreonam, delafloxacin, GSK2140944, plazomycin , tigecycline, solitromycin, etc.

Abbreviations used in the present invention include the following: ACN=acetonitrile; aq.=water; Bn=benzyl; Boc=tert-butoxycarbonyl; CDCl ₃ =deuterated chloroform; CDI=carbodiimidazole; DCE=1,2-dichloroethane; DCM=dichloromethane; DIAD=diisopropyl azodicarboxylate; DIPEA=diisopropylethylamine; DMAP=4-dimethylaminopyridine or N,N-dimethylaminopyridine; DMF=N,N-dimethylformamide; DMSO=dimethyl sulfoxide; Et=ethyl; EtOAc=ethyl acetate; H ₂ =hydrogen gas, HPLC=high performance liquid chromatography; LC-MS=liquid chromatography/mass spectrometry; Me=methyl; MeCN=acetonitrile; MeOH=methanol; MIC=minimum inhibitory concentration; MW=molecular weight; MS=mass spectrometry; Pd/C=palladium on carbon; PNB-p-nitrobenzyl; PNZ=p-nitrobenzylcarbamate; PPh ₃ =triphenylphosphine; RB=round bottom flask; RT=room temperature; TBDMS=tert-butyldimethylsilyl; TBTU= N,N,N',N' -tetramethyl- O- (benzotriazol-1-yl)uronium tetrafluoroborate; TEA=triethylamine; TFA=trifluoroacetic acid; THF=tetrahydrofuran; TLC=thin layer chromatography .

The compounds described in the present invention can be prepared according to the following reaction schemes and examples, or modifications thereof, using readily available starting compounds, reagents, and conventional methods of preparation. In these reactions, it is also possible to use variants that are themselves known to the person skilled in the art, but are not mentioned in more detail. Moreover, other methods for preparing the compounds described in the present invention will be apparent to a person skilled in the art in light of the following reaction schemes and examples.

Described below are methods for preparing a compound of formula ((I), (Ia) or (Ib) as shown in General Schemes 1, 2, 2a and 3, wherein all groups are as previously defined.

SCHEME 1

Stage 1: the compound of formula (1) was obtained according to known methods available in the literature. The reaction was carried out in the presence of a base, alkali metal carbonates such as sodium carbonate, potassium carbonate and the like, in a suitable solvent such as tetrahydrofuran (THF), dimethoxyethane, ether, dichloromethane (DCM), dimethylformamide (DMF), acetone and the like.

Step 2: The silyl group in the compound of formula (1) was removed with mineral acids such as HCl, H ₂ SO ₄ and the like in the presence of a solvent such as tetrahydrofuran, dioxane, acetonitrile (ACN), dimethylformamide and the like, to give a compound of formula (2 ).

Step 3: A compound of formula (3) was prepared by reacting a compound of formula (2) with triphenylphosphine (PPh ₃ ), formic acid and diisopropyl azodicarboxylate (DIAD) in the presence of THF.

Step 4: The compound of formula (3) was hydrolyzed according to the method described in Bull Chem Soc Japan, 1976 , 49, 510 to give a compound of formula (4).

Step 5: The compound of formula (4) is reacted with triphenylphosphine, hydrazoic acid and DIAD according to the method described in Tetrahedron Letters, 1983 , 49, 554 to give the compound of formula (5).

Step 6: reduction of the compound of formula (5) using reducing reagents such as triphenylphosphine, trimethylphosphine, triethylphosphine, tributylphosphine, methyldiphenylphosphinite or ethyldiphenylphosphinite and the like, in the presence of aqueous organic solvents such as tetrahydrofuran (THF), dioxane, acetonitrile (ACN), acetone or dimethylformamide (DMF) containing about 1%-50% water, preferably about 5%-10% water, and the like according to the known Staudinger reaction, gave the compound of formula (6).

Step 7: A compound of formula (7) was prepared by reacting an amino-protected compound of formula (6) in the presence of an organic base such as sodium bicarbonate and the like, and water-miscible solvents such as THF, dioxane and acetone, followed by hydrolysis using a base such as LiOH and the like. Suitable amino protecting groups include, for example, acyl groups such as formyl, acetyl and substituted acetyl (e.g. halogenated acetyl), benzoyl and substituted benzoyl, alkoxycarbonyl, halogenated alkoxycarbonyl, alkenyloxycarbonyl, aralkoxycarbonyl, halogenated aralkoxycarbonyl, benzyl and benzyl derivatives, trityl and trityl derivatives, sulfenyl derivatives, sulfonyl derivatives, diacyl derivatives such as phthalimido or succinimido or derivatives thereof, and Schiff bases formed from aldehydes or ketones. Carbamate protection is carried out using di-tert-butoxycarbonyl anhydride (BOC anhydride) and an inorganic base such as sodium bicarbonate in a water-miscible solvent such as tetrahydrofuran, dioxane and acetone.

Step 8: The compound of formula (7) is reacted with carbodiimidazole and magnesium mono p-nitrobenzyl malonate ester in a known manner as described in DG Melillo et al., Tetrahedron Letters, 1980 , 21, 2783, to give the compound of formula (8). The reaction of magnesium malonate with an activated carboxyl group molecule was carried out in an organic solvent such as tetrahydrofuran, dioxane, dichloromethane, acetonitrile, benzene, toluene and the like.

Step 9: The compound of formula (8) was subjected to a diazo group transfer reaction to obtain a compound of formula (9). The compound of formula (8) is treated with an azide such as dodecabenzenesulfonyl azide, 4-carboxybenzenesulfonyl azide, p-toluenesulfonyl azide, methanesulfonyl azide and the like in the presence of a base such as triethylamine (TEA), diethylamine, pyridine or lutidine and the like and a solvent such as acetonitrile, dichloromethane, toluene, benzene and the like to give a compound of formula (9).

Step 10: A compound of formula (10) was obtained by treating a compound of formula (9) with acids such as trifluoroacetic acid (TFA) or HCl and the like in the presence of solvents such as dioxane or ether and the like.

SCHEME 2

Step 11a: Reaction of a compound of formula (10) with R ^A COOH in the presence of condensing reagents such as carbodiimides, phosphonium, uronium, guanidinium salts and the like and solvents such as ethyl acetate (EtOAc) and the like gave the compound of formula (11).

Step 11b: reaction of a compound of formula (10) with R ^A X (X is Cl, Br, F, I) in the presence of acid binding agents such as alkali metal acetate, alkali metal hydroxide, calcium oxide, calcium carbonate, magnesium carbonate , or organic bases such as pyridine, N-methylmorpholine, diisopropylethylamine (DIPEA), TEA and the like, and solvents such as DCM, dioxane, toluene and the like, gave the compound of formula (11).

Step 11c: The compound of formula (10) is reacted with a carbonylating agent such as phosgene, diphosgene, triphosgene, N,N'-carbonyldiimidazole (CDI), thiophosgene, thiocarbonyldiimidazole and the like in the presence of bases such as pyridine, N-methylmorpholine, DIPEA , TEA and the like in solvents such as DCM, 1,2-dichloromethane, toluene, ACN and the like, and then treated with R ^A OH/R ^A NH ₂ to give a compound of formula (11).

SCHEME 2a

Step 11d: A compound of formula (a) is reacted with R ³ OH in the presence of triphenylphosphine and DIAD in solvents such as THF and the like to give a compound of formula (11).

Step 11e: The compound of formula (b) is reacted with compound (c) in the presence of copper iodide and DIPEA in solvents such as toluene and the like to give a compound of formula (11).

SCHEME 3

Step 12: A compound of formula (12) was prepared by reacting a compound of formula (11) with a compound of general formula H-SR ¹ , where R ¹ is as previously defined, in the presence of an activating agent such as diphenyl chlorophosphate, dimethylaminopyridine (DMAP) and the like, and a catalyst such as Cu(II) bis(acetylacetonate), copper sulfate, copper powder, rhodium acetate [Rh ₂ (OAc) ₄ ], rhodium (II) octanoate, Pd(OAc) ₂ , Pb(OAc) ₄ and the like. , and solvents such as tetrahydrofuran, ethyl acetate, benzene, toluene, hexane, cyclohexane and the like.

Step 12a: Reaction of a compound of formula (12) with 2-iodoacetamide or iodomethane and the like in the presence of solvents such as THF-acetone and the like gives a compound of formula (I), (Ia) or (Ib).

Step 13: A compound of formula (I), (Ia) or (Ib) was prepared by reacting a compound of formula (12) or a compound of formula (12a) with Pd/C in the presence of solvents such as THF-water and the like under pressure.

Step 14: Hydroxymethylation by cross-coupling reaction between carbapenem-2-triflate and Bu ₃ SnCH ₂ OH.

Step 15: allyl carbonate (14) was prepared with isobutyl chloroformate in the presence of DIPEA, DMAP and in solvents like dichloromethane and tetrahydrofuran.

Stage 16: allyl amine (15) was obtained by the reaction of allyl carbonate (14) and amine in the presence of a palladium catalyst.

Step 17: formula (Ia) was obtained by reducing the compound of formula (15) with Pt/C in the presence of solvents such as THF-water and the like under pressure.

The examples below are given for illustration only and should not be considered as limiting the scope of the present invention.

EXAMPLES

Getting 1: (R) -Benzyl 2-((2 S .3 S )-3-(( R )-1-(tert-butyldimethylsilyloxy)ethyl)-4-oxoazetidin-2-yl)propanoate

To a mixture of (R) -2-((2S,3S)-3-(( R )-1-(tert-butyldimethylsilyloxy)ethyl)-4-oxoazetidin-2-yl)propanoic acid (1 g, 3.32 mmol ), potassium carbonate (0.68 g, 4.95 mmol) and acetone (10 ml) were added benzyl bromide (0.63 g, 3.67 mmol) and refluxed for 5 hours. The reaction mixture was filtered and the residue was washed with ethyl acetate (25 ml). The organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give the title compound as an oil. (1.2 g, 92.3%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 0.01 (d, 6H), 0.79 (s, 9H), 1.04 (d, 6H), 2.37-2.46 (m, 1H ), 2.84 (t, 1H), 3.63-3.65 (d, 1H), 4.02-4.07 (m, 1H), 4.83-4.84 (m, 2H), 7.30-7.38 (m, 5H), 8.06 (s, 1H).

Getting 2 :( R )-Benzyl-2-((2 S .3 S )-3-(( R )-1-hydroxyethyl)-4-oxoazetidin-2-yl)propanoate

Aqueous hydrochloric acid (2 N, 10 mL) was added to 10 g of ( R )-benzyl-2-((2S,3S)-3-(( R )-1-(tert-butyldimethylsilyloxy)ethyl)-4-oxoazetidine- 2-yl)propanoate (10 g) dissolved in acetonitrile (100 ml) and stirred at room temperature for 3 hours. The reaction mixture was concentrated to give a crude oil which was dissolved in ethyl acetate (250 ml). The organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated in vacuo. The residue thus obtained was triturated with hexane (100 ml), filtered and dried to give the product as a white solid (6.2 g, 87.5%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.08-1.09 (d, 3H), 1.17-1.18 (d, 3H), 2.66-2.73 (m, 1H) , 2.86-2.87 (d, 1H), 3.63-3.65 (d, 1H), 3.86-3.91 (m, 1H), 4.85-4.86 (d, 1H), 5.08-5.31 (m, 2H), 7.35-7.42 (m, 5H), 8.17 (s, 1H).

Receiving 3: (R) -Benzyl 2-((2 S .3 S )-3-(( S )-1-(formyloxy)ethyl)-4-oxoazetidin-2-yl)propanoate

To a solution of (R) -benzyl 2-((2S,3S)-3-(( R) -1-hydroxyethyl)-4-oxoazetidin-2-yl)propanoate (10 g, 36.05 mmol) in tetrahydrofuran (100 ml) triphenylphosphine (15.2 g, 57.95 mmol) and 98% formic acid (3.33 g, 72.34 mmol) were added under ice-cooling conditions. Then, diisopropyl azodicarboxylate (11.7 g, 57.86 mmol) was slowly added to the reaction mixture over 15 minutes. The reaction mixture was further stirred under ice-cooling conditions for 30 minutes. Then, water (50 ml) was added and the reaction mixture was extracted with ethyl acetate (100 ml). The organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated in vacuo. The residue thus obtained was stirred with toluene (100 ml) and filtered. The filtrate was concentrated to give a crude oil. The oil thus obtained was purified by column chromatography to give the product as an oily substance (3.32 g, 30.2%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.036 (d, 3H), 1.13 (d, 3H), 2.49-2.5 (q, 1H), 2.65 (t, 1H), 2.81-2.83 (q, 1H), 3.58-3.6 (q, 1H), 3.81-3.85 (q, 1H), 4.80 (br, 1H), 5, 03-5.12 (dd, 2H), 7.30-7.38 (m, 5H), 8.12 (s, 1H).

Receiving 4: (R) -Benzyl 2-((2 S .3 S )-3-( (S) -1-hydroxyethyl)-4-oxoazetidin-2-yl)propanoate

To a solution of (R) -benzyl 2-((2S,3S)-3-(( S)- 1-(formyloxy)ethyl)-4-oxoazetidin-2-yl)propanoate (10 g, 32.75 mmol) in tetrahydrofuran (100 ml) was added lithium hydroxide (0.768 g, 32.07 mmol) dissolved in 30 ml of water under ice-cooling conditions. After completion of the reaction, the reaction mixture was concentrated and diluted with ethyl acetate (150 ml). The organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated. The crude product thus obtained was purified by column chromatography to give the product as a white solid. (8 g, 88.1%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.12 (d, 3H), 1.17 (d, 3H), 2.65-2.70 (q, 1H), 2.84 (q, 1H ), 3.48-3.51 (m, 1H), 3.81-3.85 (m, 1H), 5.09 (dd, 2H), 7.35-7.39 (m, 5H), 8.05 (s, 1H).

Receiving 5: (R) -Benzyl 2-((2 S .3 S )-3-( (R) -1-azidoethyl)-4-oxoazetidin-2-yl)propanoate

To a solution of (R) -benzyl 2-((2S,3S)-3-(( S) -1-hydroxyethyl)-4-oxoazetidin-2-yl)propanoate (10 g, 36.05 mmol) in 200 ml tetrahydrofuran :toluene (1:1) was added triphenylphosphine (15.14 g, 57.72 mmol) and 85 ml of 0.85 M hydrazoic acid (3.1 g, 72.09 mmol) at -10°C under nitrogen atmosphere. Diisopropyl azodicarboxylate (11.7 g, 57.86 mmol) was added slowly to the mixture above over 15 minutes. The mixture was further stirred under ice-cooling conditions for 30 minutes. Water (50 ml) was added to the reaction mixture and concentrated to half volume. Then, the reaction mixture was extracted with ethyl acetate (300 ml). The organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated. The residue thus obtained was stirred with toluene (100 ml) and filtered. The filtrate was concentrated to give a crude oil. The oil thus obtained was purified by column chromatography to give the product as an oily substance. (7.95 g, 72.9%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.12-1.19 (m, 6H), 2.65-2.71 (q, 1H), 3.01-3.03 (q, 1H) , 3.5-3.53 (m, 1H), 3.89-3.92 (m, 1H), 5.06-5.14 (dd, 2H), 7.33-7.39 (m, 5H), 8.37 (s, 1H).

Receiving 6: (R) -Benzyl 2-((2 S .3 R )-3-( (R) -1-aminoethyl)-4-oxoazetidin-2-yl)propanoate

Triphenylphosphine (6.51 g, 24.8 mmol) was added to a solution of (R) -benzyl 2-((2S, 3S)-3-(( R) -1-azidoethyl)-4-oxoazetidin-2-yl)propanoate (5 g, 16.6 mmol) in tetrahydrofuran (25 ml) and the mixture was stirred at room temperature for 5 hours under nitrogen. Water (5 ml) was added to the reaction mixture, and it was stirred at room temperature for 16 hours. To the reaction mixture was added brine (50 ml) and extracted with ethyl acetate (100 ml). The organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated. The residue thus obtained was stirred with toluene (100 ml) and filtered. The filtrate was concentrated to give a crude oil. The oil thus obtained was purified by column chromatography to give the product as an oily substance. (4 g, 87.5%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 0.963-0.98 (d, 3H), 1.00-1.12 (d, 3H), 2.62-2.66 (m, 1H), 2 .69-2.72 (m, 1H), 2.96-2.98 (m, 1H), 3.52-3.54 (m, 1H), 5.08-5.09 (dd, 2H) , 7.30-7.39 (m, 5H), 8.15 (s, 1H).

Receiving 7: (R) -Benzyl 2-((2 S .3 R )-3-( (R) -1-(tert-butoxycarbonylamino)ethyl)-4-oxoazetidin-2-yl)propanoate

To a mixture of sodium bicarbonate (6.1 g, 72.04 mmol) and (R) -benzyl 2-((2S,3R)-3-(( R) -1-aminoethyl)-4-oxoazetidin-2-yl) propanoate (10 g, 36.18 mmol) in 150 ml tetrahydrofuran:water (2:1) was added di-tert-butyl dicarbonate (9.5 g, 43.47 mmol) and stirred at room temperature for 6 hours. The reaction mixture was filtered and extracted with ethyl acetate (250 ml). The organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give the product as a white solid (10 g, 73.4%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.09-1.112 (m, 6H), 1.36 (s, 9H), 2.65-2.70 (m, 1H), 2.92 (m , 1H), 3.51-3.53 (m, 1H), 3.60-3.74 (m, 1H), 5.10-5.16 (dd, 2H), 6.73-6.75 (d, 1H), 7.32-7.37 (m, 5H), 8.2 (2, 1H).

Getting 8: (R) -2-((2 S .3 R )-3-( (R) -1-(tert-Butoxycarbonylamino)ethyl)-4-oxoazetidin-2-yl)propanoic acid

Lithium hydroxide (0.768 g, 32.07 mmol) was added to a solution of (R) -benzyl 2-((2S,3R)-3-(( R) -1-(tert-butoxycarbonylamino)ethyl)-4-oxoazetidine-2 -yl)propanoate (10 g, 26.56 mmol) in 50 ml tetrahydrofuran:methanol:water (1:1:0.5) under ice-cooling conditions. The reaction mixture continued to stir at room temperature for 1 hour. The reaction mixture was concentrated and diluted with water (150 ml). The aqueous layer was washed with EtOAc (150 ml). The separated aqueous layer was acidified with citric acid to pH 2 and extracted with ethyl acetate (250 ml). The organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give the product as a white solid. (7.05 g, 92.7%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.09-1.112 (m, 6H), 1.39 (s, 9H), 2.50-2.51 (m, 1H), 2.88-2 .91 (m, 1H), 3.4-3.58 (m, 1H), 3.69-3.75 (m, 1H), 6.7 (d, 1H), 8.15 (s, 1H ), 12.35 (s, 1H).

Receiving 9: (R) -4-Nitrobenzyl 4-((2 R .3 R )-3-( (R) -1-(tert-butoxycarbonylamino)ethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate

To a solution of (R) -2-((2S,3R)-3-((R)-1-(tert-butoxycarbonylamino)ethyl)-4-oxoazetidin-2-yl)propanoic acid (10 g, 34.93 mmol ) in acetonitrile (100 ml) was added 1,1'-carbonyldiimidazole (6.52 g, 40.21 mmol) and continued to stir for 1 hour under ice-cooling under nitrogen atmosphere. The above solution was slowly added to a suspension of magnesium salt of mono- p -nitrobenzylmalonate (20.32 g, 77.26 mmol) in acetonitrile (100 ml) and stirred for 5 hours at room temperature and heated at 50 °C for an additional 6 hours in a nitrogen atmosphere. The reaction mixture was filtered and the filtrate was concentrated and the resulting crude residue was diluted with ethyl acetate. The organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give a crude oil. The oil thus obtained was purified by column chromatography to give the product as a white solid (10 g, 61.78%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.09-1.112 (m, 6H), 1.39 (s, 9H), 2.87-2.91 (m, 1H), 2.99-3 .00 (m, 1H), 3.5-3.52 (m, 1H), 3.73-3.77 (m, 1H), 3.8-3.93 (dd, 2H), 5.29 (s, 2H), 6.7 (d, 1H), 7.60-7.66 (d, 2H), 8.09 (s, 1H), 8.23-8.26 (d, 2H).

Getting 10: (R) -4-Nitrobenzyl 4-((2 R .3 R )-3-( (R) -1-(tert-butoxycarbonylamino)ethyl)-4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate

To a solution of (R) -4-nitrobenzyl 4-((2R,3R)-3-(( R)- 1-(tert-butoxycarbonylamino)ethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate (10 g , 21.57 mmol) in acetonitrile (50 mL) were added successively dodecabenzenesulfonyl azide (70% in toluene, 13 mL, 25.9 mmol) and triethylamine (12.7 mL, 91.1 mmol) under ice-cooling conditions. The reaction mixture was stirred for 1 hour, and then it was concentrated and diluted with ethyl acetate (150 ml). The organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give a crude oil. The oil thus obtained was purified by column chromatography to give the product as a white solid (10 g, 94.69%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.00-1.02 (d, 3H), 1.06-1.08 (d, 3H), 1.39 (s, 9H), 3.01 -3.03(m, 1H), 3.47-3.49(m, 1H), 3.63-3.66(m, 1H), 3.71-3.73(m, 1H), 5 .43 (s, 2H), 6.55 (d, 1H), 7.69-7.72 (d, 2H), 8.15 (s, 1H), 8.25-8.27 (d, 2H ).

Receiving 11: (R) -4-Nitrobenzyl 4-((2 R .3 R )-3-( (R) -1-aminoethyl)-4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate

Trifluoroacetic acid (1.40 g, 12.3 mmol) was added to a solution of (R) -4-nitrobenzyl 4-((2R, 3R)-3-((R)-1-(tert-butoxycarbonylamino)ethyl)-4 -oxoazetidin-2-yl)-2-diazo-3-oxopentanoate (2 g, 4.08 mmol) in dichloromethane (10 ml) under ice-cooling and stirred for 2 hours under nitrogen atmosphere. The reaction mixture was concentrated and the resulting residue triturated with diethyl ether to give the product as a white solid.

Getting 12:2-( (Z) -one-( (R) -1-((2 R .3 R )-2-( (R) -4-diazo-5-(4-nitrobenzyloxy)-3,5-dioxopentan-2-yl)-4-oxoazetidin-3-yl)ethylamino)-1-oxopropan-2-ylideneaminooxy)-2-methylpropanoic acid

Mixture of (Z) -2-(2-methyl-1-(4-nitrobenzyloxy)-1-oxopropan-2-yloxyimino) propanoic acid (1 g, 3.08 mmol), tetrafluoroborate N,N,N',N' -tetramethyl- O- (benzotriazol-1-yl)uronium (TBTU) (1.19 g, 3.7 mmol), diisopropylethylamine (1.1 ml, 6.32 mmol) and ethyl acetate (50 ml) were stirred at room temperature for 30 minutes under nitrogen atmosphere. (R)-4-nitrobenzyl 4-((2R, 3R)-3-((R)-1-aminoethyl)-4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate (1 .2 g, 3.08 mmol) and stirred for an additional 30 minutes. The reaction mixture was treated with water (20 ml) and extracted with EtOAc (50 ml). The separated organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give the product as an off-white solid. ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.47-1.49 (m, 9H), 1.55 (s, 3H), 2.06-2.08 (d, 1H), 3.06 (t, 1H), 3.64-3.72 (d, 1H), 4.31-4.34 (q, 1H), 5.43 (s, 4H), 7.29-7.34 (s , 2H), 7.70-7.77 (dd, 4H), 8.25-8.32 (dd, 4H).

Receipt 13: (R) -4-Nitrobenzyl 2-diazo-4-((2 R .3 S )-3-( (R) -1-(methylsulfamido)ethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate

Methanesulfonyl chloride (0.19 ml, 25.7 mmol) was added to a mixture of (R) -4-nitrobenzyl 4-((2R,3R)-3-(( R) -1-aminoethyl)-4-oxoazetidin-2-yl )-2-diazo-3-oxopentanoate (1 g, 2.57 mmol) and diisopropylethylamine (0.92 ml, 51.4 mmol) in dichloromethane (20 ml) under ice-cooling under nitrogen atmosphere. The reaction mixture was treated with water (20 ml) and extracted with dichloromethane (50 ml). The separated organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give a crude residue which, after purification by column chromatography, gave the product as an off-white solid. ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.14-1.18 (d, 3H), 1.19-1.22 (d, 3H), 2.85-2.89 (d, 1H) , 2.91 (s, 3H), 3.52-3.57 (m, 2H), 3.69-3.72 (m, 1H), 5.39-5.47 (dd, 2H), 7 .08-7.10 (d, 1H), 7.70-7.72 (d, 2H), 8.25-8.27 (dd, 3H).

Getting 14 :(R) -4-Nitrobenzyl 2-diazo-4-((2 R .3 R )-3-( (R) -1-(methoxycarbonylamino)ethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate

Methyl chloroformate (0.2 ml, 2.58 mmol) was added to a mixture of (R) -4-nitrobenzyl-4-((2R,3R)-3-(( R) -1-aminoethyl)-4-oxoazetidine-2- yl)-2-diazo-3-oxopentanoate (1 g, 2.57 mmol) and diisopropylethylamine (0.92 ml, 51.4 mmol) in dichloromethane (20 ml) under ice-cooling under nitrogen atmosphere. The reaction mixture was treated with water (20 ml) and extracted with dichloromethane (50 ml). The separated organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give a crude residue which, after column purification, gave an off-white solid. ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.01-1.02 (d, 3H), 1.06-1.09 (d, 3H), 2.82-2.85 (d, 1H) , 3.44-3.48(m, 1H), 3.49(s, 3H), 3.65-3.69(m, 2H), 5.41-5.44(m, 2H), 7 .10-7.12 (d, 1H), 7.69-7.73 (d, 2H), 8.25-8.27 (m, 3H).

Getting 15: (R) -4-Nitrobenzyl 2-diazo-4-((2 R .3 R )-3-( (R) -1-(methoxycarbonothioylamino)ethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate

To an ice-cold solution of (R) -4-nitrobenzyl 4-((2R,3R)-3-(( R) -1-aminoethyl)-4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate ( 1 g, 2.57 mmol) in dichloromethane (10 ml) was added an aqueous solution of NaHCO ₃ (0.6 g in 10 ml, 7.14 mmol). Thiophosgene (0.25 ml, 3.34 mmol) was added to the mixture above and stirred for 1 hour. After completion of the reaction, the reaction mixture was filtered. The organic layer was washed with water and evaporated to give the crude product. The oil thus obtained was purified by column chromatography. The resulting compound was dissolved in methanol (10 ml) and refluxed for 5 hours. The reaction mixture was evaporated and purified by column chromatography to give the title compound. ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.10-1.15 (d, 3H), 1.21-1.22 (d, 3H), 2.00 (d, 1H), 2.88 -2.89 (d, 1H), 3.50-3.51 (m, 1H), 3.61-3.62 (s, 3H), 3.68-3.70 (m, 1H), 5 .42 (m, 2H), 6.89-6.90 (d, 1H), 7.70-7.75 (d, 2H), 8.24-8.26 (d, 2H), 8.34 (s, 1H).

Getting 16: (R) -4-Nitrobenzyl 2-diazo-4-((2 R .3 R )-3-((R)-1-(2-methoxy-2-oxoacetamido)ethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate

Mixture of 2-methoxy-2-oxoacetic acid (0.14 g, 1.35 mmol), N,N,N',N' -tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (TBTU, 0.43 g, 1.35 mmol) and diisopropylethylamine (0.25 ml, 1.46 mmol) in ethyl acetate (10 ml) were stirred for 30 minutes. To the reaction mixture above was added a solution of (R) -4-nitrobenzyl 4-((2R, 3R)-3-(( R) -1-aminoethyl)-4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate (0.6 g, 1.22 mmol) in ethyl acetate (5 ml) and stirred for 2 hours. After completion of the reaction, the reaction mixture was diluted with water. The organic layer was separated and washed successively with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give a crude residue which, after purification by column chromatography, gave the product as an oily substance. (0.25g-42.8%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.11-1.18 (d, 3H), 1.20-1.21 (d, 3H), 2.08 (d, 1H), 2.86 -2.88 (d, 1H), 3.50-3.51 (m, 1H), 3.61-3.62 (s, 3H), 3.65-3.70 (m, 1H), 5 .42 (m, 2H), 6.91-6.96 (d, 1H), 7.70-7.71 (d, 2H), 8.22-8.25 (d, 2H), 8.13 (s, 1H).

Receipt 17: (R) -4-Nitrobenzyl 2-diazo-4-((2 R .3 R )-3-( (R) -1-(2,2-difluoroacetamido)ethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate

Following the method presented in Preparation 16, (R) -4-nitrobenzyl 4-((2R,3R)-3-(( R) -1-aminoethyl)-4-oxoazetidin-2-yl)-2-diazo-3 -oxopentanoate (5 g, 12.84 mmol) was derivatized with difluoroacetic acid to give the title product (3.7 g, 78.7%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.10-1.12 (d, 3H), 1.21-1.23 (d, 3H), 2.06 (d, 1H), 2.87 -2.91(d, 1H), 3.51-3.55(m, 1H), 3.67-3.69(m, 1H), 5.43(m, 2H), 6.94-6 .96 (t, 1H), 7.70-7.72 (d, 2H), 8.14-8.16 (d, 2H), 8.20 (s, 1H).

Preparation 18: (R)-4-nitrobenzyl 4-((2R,3R)-3-((R)-1-cyanoamidoethyl)-4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate

Cyanogen bromide (0.14 g, 1.28 mmol) was added to a solution of (R)-4-nitrobenzyl 4-((2R,3R)-3-((R)-1-aminoethyl)-4-oxoazetidin-2-yl )-2-diazo-3-oxopentanoate (0.5 g, 1.28 mmol) in dichloromethane (10 ml) under ice-cooling conditions. Triethylamine (0.3 ml, 2.15 mmol) was added to the mixture above and stirred under ice-cooling for 1 hour. After completion of the reaction, the reaction mixture was treated with water. The organic layer was separated and washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give a crude residue which, after purification by column chromatography, gave the product as a white solid (0.33 g, 62%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.11-1.18 (d, 3H), 1.21-1.23 (d, 3H), 2.08 (d, 1H), 2.87 -2.89 (d, 1H), 3.51-3.54 (q, 1H), 3.68-3.71 (q, 1H), 5.43 (s, 2H), 6.95-6 .96 (d, 1H), 7.69-7.71 (d, 2H), 8.24-8.26 (d, 2H), 8.34 (s, 1H).

Getting 19 :( R )-2-diazo-4-((2 R .3 S )-3-((R)-1-(isoxazol-3-yloxy)ethyl)-4-oxoazetidin-2-yl)-3-oxopentane 4-nitrobenzoic anhydride

To a solution of (R)-4-nitrobenzyl 2-diazo-4-((2R,3S)-3-((S)-1-hydroxyethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate (2.15 g, 5.34 mmol) in tetrahydrofuran (10 ml) was added triphenylphosphine (2.24 g, 8.54 mmol) and isoxazol-3-ol (0.9 g, 10.62 mmol) at 0 °C. Diisopropyl azodicarboxylate (1.73 g, 8.56 mmol) was added slowly at 0° C. over 10 minutes. The reaction mixture was stirred for 5 hours at room temperature. After completion of the reaction (as measured by TLC), the reaction mixture was diluted with ethyl acetate (25 ml) and washed with water (25 ml) and brine (25 ml). The organic layer was dried over sodium sulfate and the solvent was evaporated to give the crude residue as an oil. The crude product was treated with toluene (10 ml) and stirred at 0°C for 30 minutes, filtered and washed with 10 ml of toluene (cold). The filtrate and washings were mixed together and concentrated to give the crude product. The crude product after purification by column chromatography (15% EtOAc in hexane) gave the title product (0.9 g, 34.6%).

Preparation 20: (R)-4-nitrobenzyl 2-diazo-4-((2R,3S)-3-((R)-1-(4-(((4-nitrobenzyloxy)carbonylamino)methyl)-1H-1 ,2,3-triazol-1-yl)ethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate

Mixture of (4R)-4-nitrobenzyl 4-(3-((R)-1-azidoethyl)-4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate (1 g, 2.41 mmol), 4 -nitrobenzyl prop-2-ynylcarbamate (0.56 g, 2.41 mmol) and copper iodide (0.09 g, 0.48 mmol) in toluene (10 ml) was stirred for 18 hours. The solvent was evaporated and the resulting crude product was purified by flash chromatography to give the title compound. (eluted with 6% acetone-DCM).

Preparation 21: (R)-4-nitrobenzyl 2-diazo-4-((2R,3R)-3-((R)-1-(2-(methyl((4-nitrobenzyloxy)carbonyl)amino)acetamido)ethyl )-4-oxoazetidin-2-yl)-3-oxopentanoate

To a mixture of p-nitrobenzyloxycarbonylsarcosine (10 g, 37.28 mmol) and diisopropylethylamine (9.3 ml, 56.26 mmol) in ethyl acetate (60 ml) was added TBTU (14.36 g, 44.72 mmol) and stirred for 0.5 hours at room temperature. Solution of (R)-4-nitrobenzyl 4-((2R,3R)-3-((R)-1-aminoethyl)-4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate (14.5 g , 37.24 mmol) in EtOAc (25 ml) was added to the mixture above at 0°C and the reaction mixture was stirred for 3 hours at room temperature. After completion of the reaction, the reaction mixture was diluted with EtOAC (150 ml) and washed with water and brine. The organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure to give the crude product as an oil. The crude product, after purification by column chromatography (20% acetone in dichloromethane), gave the title compound as a pale yellow solid (10.7 g, 65%).

Preparation 22: iodide 1-(2-amino-2-oxoethyl)-1-methyl-4-((2S,4S)-4-((4R,5S,6S)-4-methyl-6-((R) -1-(methylsulfamido)ethyl)-2-((4-nitrobenzyloxy)carbonyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-ylthio)-1-((4 -nitrobenzyloxy)carbonyl)pyrrolidine-2-carbonyl)piperazin-1-ium

(4R,5S,6S)-4-nitrobenzyl 4-methyl-3-((3S,5S)-5-(4-methylpiperazine-1-carbonyl)-1-((4-nitrobenzyloxy)carbonyl)pyrrolidine-3- ylthio)-6-((R)-1-(methylsulfamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate (0.5 g, 0.6 mmol) was dissolved in tetrahydrofuran (2 ml) and acetone (5 ml). 2-Iodoacetamide (0.55 g, 2.97 mmol) was added to the reaction mixture and refluxed for 4 hours. The reaction mixture was concentrated in vacuo and triturated with ethyl acetate (10 ml) to give a solid residue. The resulting solid was filtered and dried to give the product as an off-white solid. (0.36 g, 60%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.15-1.19 (d, 3H), 1.24-1.28 (d, 3H), 2.92 (s, 3H), 3.16 -3.29(m, 2H), 3.54-3.57(s, 2H), 3.61-3.66(m, 4H), 3.73-3.82(m, 4H), 3 .86-3.91 (m, 3H), 4.0-4.03 (m, 3H), 4.15-4.23 (m, 4H), 5.21-5.47 (m, 4H) , 7.33-7.35 (d, 1H), 7.52-7.54 (d, 1H), 7.64-7.66 (d, 1H), 7.69-7.71 (d, 1H), 7.76-7.79 (d, 1H), 8.22-8.24 (4H).

Preparation 23: (R)-4-nitrobenzyl 2-diazo-4-((2R,3R)-3-((R)-1-(2-ethoxy-2-oxoethylamino)ethyl)-4-oxoazetidine-2- yl)-3-oxopentanoate

Ethyl bromoacetate (0.342 g, 2.05 mmol) was added to a mixture of (R) -4-nitrobenzyl 4-((2R, 3R)-3-(( R) -1-aminoethyl)-4-oxoazetidin-2-yl) solution -2-diazo-3-oxopentanoate (1 g, 2.05 mmol), diisopropylethylamine (0.45 ml, 2.58 mmol) and catalytic amounts of dimethylaminopyridine in dichloromethane (15 ml) at 0°C and stirred for 16 hours at room temperature. After standard work-up, the resulting crude residue was purified by chromatography to give the title compound (0.37 g, 30%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.08 (d, 3H), 1.12 (d, 3H), 1.29 (t, 3H), 2.85 (d, 1H), 3, 40-3.42(m, 1H), 3.63-3.66(m, 1H), 3.77(s, 2H), 3.99(m, 1H), 4.13(q, 2H) , 5.44 (s, 2H), 8.25 (m, 2H), 8.32 (s, 2H).

Preparation 24: (R)-4-nitrobenzyl 4-((2R,3S)-3-((R)-1-(butyl((4-nitrobenzyloxy)carbonyl)amino)ethyl)-4-oxoazetidin-2-yl )-2-diazo-3-oxopentanoate

Step (i): solution of a mixture of 1-bromobutane (0.56 g, 4.09 mmol) and (R) -4-nitrobenzyl 4-((2R, 3R)-3-(( R)- 1-aminoethyl)- 4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate (1 g, 2.05 mmol) in dimethylformamide (20 ml) was heated at 50-55° C. for 16 hours. After standard work-up, the resulting crude residue was purified by chromatography to give (R)-4-nitrobenzyl 4-((2R,3R)-3-((R)-1-(butylamino)ethyl)-4-oxoazetidin-2-yl) -2-diazo-3-oxopentanoate (0.5 g, 43.7%). ¹ H NMR (CDCl ₃ ) δ ppm: 0.93 (t, 3H), 1.27 (m, 6H), 1.42 (m, 3H), 1.60 (m, 3H), 2.88 ( d, 1H), 3.42 (m, 1H), 3.74 (m, 1), 3.80 (m, 1H), 5.35 (s, 2H), 6.01 (s, 1H), 7.53 (m, 2H), 8.25 (m, 2H).

Step (ii): 4-nitrobenzyl chloroformate (0.42 g, 1.96 mmol) was added to a mixture of a solution of (R)-4-nitrobenzyl 4-((2R,3R)-3-((R)-1-(butylamino) ethyl)-4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate (0.5g, 1.12mmol), triethylamine (0.34g, 2.45mmol) and a catalytic amount of dimethylaminopyridine at 0°C and stirred at room temperature for 16 hours. After standard work-up, the resulting crude residue was purified by column chromatography to give the title compound (0.31 g, 44.2%). ¹ H NMR (DMSO-d ₆ ) δ ppm: 0.84 (t, 3H), 1.1 (d, 3H), 1.26 (m, 6H) 1.50 (m, 3H), 3.08 (m, 1H), 3.47 (m, 1H), 3.56 (m, 1), 4.01 (m, 1H), 5.19 (dd, 2H), 5.34 (s, 2H) , 7.60 (m, 2H), 7.67 (m, 2H), 8.24 (m, 4H).

Preparation 25: ethyl 2-pivalamidoacetate

O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU, 70.8 g, 0.22 mol) was added to a mixture of pivalic acid (15 g, 0.147 mol) and triethylamine (35 ml, 0.25 mol) in ethyl acetate (150 ml) and stirred for 0.5 hour at room temperature. Glycine ethyl ester HCl (20.52 g, 0.147 mol) was added to the mixture above at 0° C. and the reaction mixture was stirred for 16 hours at room temperature. After completion of the reaction, the reaction mixture was diluted with EtOAC (150 ml) and washed with water and brine. After drying over sodium sulfate, the organic layer was evaporated under reduced pressure to give the crude product as an oil. The crude residue after purification by column chromatography (10% MeOH in dichloromethane) gave the title compound as an off-white solid residue. (18.4 g, 67%). ¹ H NMR (CDCl ₃ ) δ=1.26 (s, 9H), 1.41 (t, 3H), 4.01 (m, 2H), 4.23 (q, 2H), 6.17 (br s, 1H).

Preparation 26: Ethyl 2-(5-tert-butyl-1H-tetrazol-1-yl)acetate

A solution of ethyl 2-pivalamidoacetate (10 g, 0.053 mol) in acetonitrile (200 ml) was treated with sodium azide (14 g, 0.22 mol) and tetrachlorosilane (10 ml, 0.087 mol). The solution was heated to 90° C. under nitrogen for 16 hours. Additional sodium azide (7 g, 0.1 mol) and tetrachlorosilane (6 ml, 0.052 mol) were added and reflux continued for an additional 16 hours. The reaction mixture was poured into chilled 5% aqueous sodium bicarbonate solution and extracted with ethyl acetate (150 ml×3). The organic layers were combined, dried over sodium sulfate, filtered and concentrated to give a crude solid (1.68 g). The solid residue was purified by column chromatography to give the product as an oil (9.5 g, 83.8%) ¹ H NMR (CDCl ₃ ) δ-1.29 (t, 3H), 1.47 (s, 9H), 4 .27 (q, 2H), 5.24 (s, 2H).

Preparation 27: 2-(5-T-butyl-1H-tetrazol-1-yl)acetic acid

At 0°C, a solution of ethyl 2-(5-tert-butyl-1H-tetrazol-1-yl)acetate (9 g, 0.042 mol) in tetrahydrofuran-MeOH (90 ml: 45 ml) was treated with a solution of lithium hydroxide monohydrate (2, 68 g, 0.064 mol) in 45 ml of water. The reaction mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was neutralized with 1N HCl to pH=6-7 and concentrated. The crude residue was treated with aqueous lithium hydroxide (2.6 g in 100 ml) and washed with ethyl acetate (150 ml). The aqueous layer was acidified with 1N HCl to pH 2 and was extracted with ethyl acetate (2×100 ml). The combined organic layers were washed with brine (150 ml). The organic layer was evaporated after drying over sodium sulfate to give the title product as a white solid (6.8 g, 87%). ¹ H NMR (DMSO-d ₆ ) δ=1.39 (s, 9H), 5.46 (s, 2H), 13.78 (br s, 1H).

Example fourteen R ,5 S .6 S )-3-((3 S ,5 S )-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-( (R) -1-(methylsulfamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid

Stage 1: (4 R ,5 S .6 S )-4-Nitrobenzyl 3-((3 S ,5 S )-5-(dimethylcarbamoyl)-1-((4-nitrobenzyloxy)carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-( (R) -1-(methylsulfamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate

To a solution of (R) -4-nitrobenzyl-2-diazo-4-((2R,3S)-3-(( R)- 1-(methyl sulfamido)ethyl)-4-oxoazetidin-2-yl)-3- oxopentanoate (preparation 13) in acetone (10 ml) was added rhodium octanoate (0.008 g, 0.01 mmol) and refluxed for 1 hour. The reaction mixture was cooled to room temperature and then to -50--40°C using an acetone-dry ice bath. Diisopropylethylamine (0.25 ml, 1.43 mmol), a catalytic amount of dimethylaminopyridine and diphenyl chlorophosphate (0.26 ml, 1.28 mmol) were added sequentially to the reaction mixture and stirred for 30 minutes at -50--40°C. (2S, 4S)-4-nitrobenzyl-2-(dimethylcarbamoyl)-4-mercaptopyrrolidine-1-carboxylate (0.374 g, 1.06 mmol) and diisopropylethylamine (0.25 ml, 1.43 mmol) were added to the reaction mixture and continued stirring at -20°C for 1 hour. Then, the reaction mixture was heated to 0°C, and stirring was continued for an additional 3 hours. The reaction mixture was treated with water (20 ml) and extracted with ethyl acetate (50 ml). The separated organic layer was washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give a crude residue which, after purification by column chromatography, gave a white solid residue of 0.4 g - 48% (compound was eluted with 20-30% acetone in dichloromethane). ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.14-1.18 (d, 6H), 1.6-1.8 (m, 1H), 2.83-2.86 (m, 3H) , 2.94(m, 1H), 2.99-3.01(d, 3H), 3.20(m, 1H), 3.40-3.43(m, 1H), 3.59-3 .61 (m, 2H), 3.88-4.22 (m, 3H), 4.23-4.27 (m, 2H) 4.78-4.88 (m, 1H), 5.09- 5.32 (d, 2H), 5.43-5.47 (d, 1H), 5.47-5.5 (d, 1H), 7.20-7.21 (d, 1H), 7. 55-7.57 (d, 1H), 7.66-7.68 (d, 1H), 7.73-7.75 (m, 2H), 8.13-8.15 (d, 1H), 8.25-8.27 (m, 4H).

Stage 2: (4 R ,5 S .6 S )-3-((3 S ,5 S )-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-( (R) -1-(methylsulfamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid

A solution of (4R,5S,6S)-4-nitrobenzyl 3-((3S,5S)-5-(dimethylcarbamoyl)-1-((4-nitrobenzyloxy)carbonyl)pyrrolidin-3-ylthio)-4-methyl-6- (( R) -1-(methylsulfamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (0.2 g, 0.258 mmol) prepared in step 1 , in THF:water (15 ml, 1:1) was subjected to hydrogenation in the presence of Pd/C. The reaction mixture was filtered through celite. The filtrate was washed with EtOAc (30 ml x 6). Then, the aqueous layer was lyophilized to give the title compound as a white solid (90 mg, 75%). ¹ H NMR (D ₂ O) δ ppm: 1.21-1.23 (d, 3H), 1.33-1.39 (d, 3H), 1.92-1.96 (m, 1H), 2.99-3.00 (s, 3H), 3.01-3.03 (m, 1H), 3.11 (m, 1H), 3.47 (s, 6H), 3.46-3, 48 (m, 2H), 3.97-3.99(m, 2H), 4.03-4.21 (d, 1H), 4.73-4.75 (d, 1H), 4.8- 4.86(d, 1H). MS m/z: 460.7.

Examples 2-6, 17, 21, 26, 28, 31, 32, 35, 37-38, 40, 42-46, 49-50, 53-56, 58-68, 70-85 and 87-94 were obtained by processing compounds of formula (10) suitable R ^A COOH according to the method indicated in preparations 12, 16 and 17, followed by the method indicated in example 1.

Examples 7-16, 18-19, 23-25, 27, 29-30, 33-34, 39, 48, 51, 57 and 86 were prepared by treating the compound of formula (10) with the appropriate R ^A X according to the method described in Preparation 13 and 14, followed by the method indicated in example 1.

Examples 20, 22, 36, 41, 47, 52 and 69 were prepared by treating the compound of formula (10) with suitable carbonylating agents according to the method of Preparation 15, followed by the method of Example 1. Quaternization of the heterocyclic rings in Examples 39, 45, 46, 80 and 94 were carried out according to the method indicated in preparation 19.

Example Structure Analytical data 2

(4R,5S,6R)-3-((3S,5S)-5-(Диметилкарбамоил)пирролидин-3-илтио)-4-метил-7-оксо-6-((S)-1-(2-(тиофен-2-ил)ацетамидо)этил)-1-азабицикло[3,2,0]гепт-2-ен-2-карбоновая кислота

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((S)-1-(2-( thiophen-2-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.12 (d, 1H), 1.29 (d, 3H), 1.33 (d, 3H), 1.36 (d, 2H), 1.98 (m, 1H), 2.99 (s, 3H), 3.06 (s, 3H), 3.19 (m, 1H), 3.41 (t, 1H), 3.85 (m, 1H) , 3.98 (m, 1H), 4.24 (m, 1H), 4.51 (d, 1H), 4.78 (d, 1H), 4.79-4.83 (m, 1H), 7.02-7.03(q, 1H), 7.16(d, 1H) 7.42(d, 1H). MS m/z: 505.1 (M-1). 3

(4R,5S,6R)-6-((R)-1-((Z)-2-(2-Carboxypropan-2-yloxyimino)propanamido)ethyl)-3-((3S,5S)-5-( dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.39 (d, 3H), 1.48 (d, 3H), 1.58 (d, 6H), 2.04 (s, 3H), 2.99 (d, 3H), 3.08 (d, 6H), 3.41-3.45 (m, 2H), 3.61 (d, 1H), 3.73-3.78 (m, 1H), 4.0 (t, 2H), 4.54-4.58 (m, 1H). MS m/z: 552 (M ^- 1) four

(4R,5S,6R)-6-((S)-1-((Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetamido)ethyl)- 3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.25 (d, 3H), 1.34 (d, 3H), 1.36 (s, 3H), 1.50 (s, 3H), 1.92 (m, 1H), 2.23 (m, 1H), 2.97 (s, 3H), 2.99 (d, 1H), 3.02 (s, 3H), 3.36-3.42 ( q, 2H), 3.50-3.76 (m, 2H), 4.03-4.23 (m, 2H), 4.82-4.88 (d, 1H), 6.98 (s, 1H). MS m/z: 637.8 5

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(2-( thiophen-2-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.27 (d, 3H), 1.32 (d, 3H), 1.96-2.04 (m, 1H), 2.96 (d, 1H) , 3.00 (s, 4H), 3.07 (s, 4H), 3.41-3.45 (m, 2H), 3.71-3.77 (m, 1H), 3.80-3 .85 (m, 1H), 3.99-4.03 (m, 1H), 4.36 (s, 2H), 4.54-4.57 (m, 1H), 7.09 (t, 1H ), 7.15 (d, 1H) 7.48 (d, 1H). MS m/z: 506.6 6

(4R,5S,6R)-6-((R)-1-((Z)-2-(2-Carboxypropan-2-yloxyimino)propanamido)ethyl)-3-((3S,5S)-5-( dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.40 (d, 3H), 1.45 (d, 3H), 1.58 (d, 6H), 2.05 (s, 3H), 2.99 (d, 3H), 3.08 (s, 3H), 3.10 (s, 3H), 3.42-3.49 (m, 1H), 3.61 (d, 1H), 3.74- 3.78 (m, 2H), 3.96-4.07 (dd, 2H), 4.51-4.73 (m, 1H). MS m/z: 553.7 7

(4R,5S,6S)-4-Methyl-6-((R)-1-(methylsulfamido)ethyl)-7-oxo-3-((3S,5S)-5-((sulfamoylamino)methyl)pyrrolidine- 3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.22-1.25 (d, 3H), 1.37-1.39 (d, 3H), 1.73-1.76 (m, 1H), 2.71-2.75(m, 1H), 3.11(s, 3H), 3.14(s, 3H), 3.35-3.55(m, 2H), 3.90-3, 91 (d, 1H), 3.99-4.02 (m, 2H), 4.20-4.23 (d, 1H), 4.79-4.85 (d, 1H). MS m/z: 497.6 eight

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((S)-1-(methylsulfamido)ethyl)-7- oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.24 (d, 3H), 1.36 (d, 3H), 1.94 (m, 1H), 2.96 (s, 3H), 2.97 (m, 1H) 3.07 (m, 1H), 3.14 (m, 1H), 3.36-3.43 (m, 6H), 3.61 (m, 2H), 3.68 (m , 1H), 3.93 (t, 1H), 4.01 (m, 1H), 4.23 (d, 1H). MS m/z: 460.7 9

(4R,5S,6S)-6-((R)-1-(3,4-Dimethoxyphenylsulfamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4- methyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.13 (m, 6H), 1.92 (m, 1H), 3.01 (s, 3H), 3.02 (m, 1H) 3.08 ( s, 3H), 3.08 (m, 1H) 3.34-3.41 (m, 1H), 3.81 (m, 1H), 3.92 (d, 1H), 3.94 (d, 2H), 3.96 (d, 6H), 4.75 (d, 2H), 7.23 (d, 1H), 7.47 (s, 1H) 7.61 (d, 1H). MS m/z: 582.6 ten

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(ethylsulfamido)ethyl)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.21 (t, 3H), 1.37-1.38 (d, 6H), 1.92-1.97 (m, 2H), 2.99-3.00 (s, 3H), 3.23 (s, 3H), 3.21-3.26 (m, 2H), 3.42-3.44 (m, 2H), 3, 67-3.74 (d, 1H), 3.76 (d, 1H), 3.92-3.95 (m, 2H), 4.02-4.03 (d, 1H), 4.23- 4.25 (d, 1H). MS m/z: 474.6 eleven

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(phenylsulfamido)ethyl )-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.09-1.14 (m, 6H), 1.93 (d, 1H), 3.00 (s, 3H), 3.13 (s, 3H) , 3.15 (d, 1H) 3.41 (d, 2H), 3.68 (t, 1H), 3.87 (t, 1H), 3.99 (d, 2H), 4.71 (d , 1H), 4.94 (d, 1H), 7.65-7.69 (t, 2H) 7.75 (d, 1H), 7.96 (d, 2H). MS m/z: 522.7 12

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(4-fluorophenylsulfamido)ethyl)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.09-1.10 (d, 3H), 1.14-1.16 (d, 3H), 1.92-1.94 (s, 1H), 3.00-3.02 (d, 3H) 3.03 (m, 1H), 3.04-3.07 (s, 3H) 3.08 (m, 1H) 3.20-3.21 (t , 1H), 3.40-3.42 (d, 2H), 3.66-3.69 (m, 1H), 3.70-3.85 (m, 1H), 4.10-4.04 (m, 2H), 7.37-7.41 (m, 2H), 7.97-8.00 (m, 2H). MS m/z: 540.7 13

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(trifluoromethylsulfamido)ethyl )-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.22-1.23 (d, 3H), 1.37-1.39 (d, 3H), 1.99-2.01 (m, 2H), 3.00-3.01 (s, 3H), 3.12 (s, 3H), 3.47-3.48 (m, 1H), 3.61-3.63 (d, 1H), 3, 72-3.77 (d, 1H), 4.06-4.17 (m, 1H), 4.19-4.20 (m, 1H), 4.47-4.50 (m, 3H). MS m/z: 513.1 (M-1). fourteen

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(methoxycarbonylamino)ethyl)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.27-1.29 (d, 3H), 1.96-1.97 (m, 1H), 3.00 (s, 3H), 3.07 (s, 3H), 3.31 (m, 2H), 3.43-3.46 (m, 2H), 3.66 (s, 3H), 4 .03 (m, 2H), 4.15-4.17 (m, 2H), 4.53 (m, 1H). MS m/z: 439 (M-1) fifteen

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(ethoxycarbonylamino)ethyl)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.27-1.29 (d, 3H), 1.96-1.97 (m, 2H), 3.00 (s, 3H), 3.07 (s, 3H), 3.31 (m, 2H), 3.43-3.46 (m, 2H), 3.66 (s, 3H), 4 .03 (m, 3H), 4.15-4.17 (m, 2H), 4.53 (m, 1H). MS m/z: 455.7 (M+1) 16

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(phenylmethylsulfamido)ethyl )-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19 (s, 3H), 1.31-1.32 (d, 3H), 1.90-1.93 (m, 1H), 3.00- 3.03 (s, 3H), 3.07-3.08 (s, 3H) 3.09 (m, 1H) 3.29-3.33 (m, 2H), 3.33 (m, 1H) , 3.64 (m, 1H), 3.66-3.69 (m, 1H), 3.86-3.89 (m, 1H), 3.99-4.00 (m, 1H), 4 .13-4.16 (m, 1H), 4.54 (s, 2H), 7.49 (m, 5H). MS m/z: 537.2 (M+1) 17

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(1-( trifluoromethyl)cyclopropanecarboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19 (d, 3H) 1.27 (d, 3H), 1.35 (m, 4H), 2.86 (m, 1H) 2.98 (s , 3H), 3.07 (s, 3H), 3.23 (m, 1H), 3.34 (d, 2H), 3.54 (d, 1H), 3.89 (d, 1H), 4 .12 (d, 2H), 4.40 (d, 2H). MS m/z: 519.1 (M+1) eighteen

(4R,5S,6S)-6-((R)-1-(Butylsulfamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.8-0.9 (m, 3H), 1.28 (d, 3H) 1.34-1.39 (m, 3H), 1.42 (m , 2H), 1.68 (m, 2H) 1.8 (s, 3H), 2.70 (m, 1H), 2.88 (s, 3H), 2.97 (s, 3H), 3, 12-3.18 (m, 4H), 3.37-3.39 (m, 2H), 4.10-4.15 (m, 2H). MS m/z: 503.2 (M+1) 19

(4R,5S,6S)-4-Methyl-7-oxo-3-((3S,5S)-5-((sulfamoylamino)methyl)pyrrolidin-3-ylthio)-6-((R)-1-( trifluoromethylsulfamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.25 (s, 3H), 1.39 (s, 3H), 1.62 (m, 1H), 1.92 (m, 1H), 2.62 (m, 1H), 3.2 (d, 1H), 3.40 (m, 2H) 3.50 (m, 1H), 3.60 (m, 1H), 3.7 (m, 1H), 3.90 (m, 1H) 4.10 (d, 1H), 4.20 (m, 1H). MS m/z: 552 (M+1) twenty

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(ethoxycarbonothioylamino)ethyl)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.25-1.42 (m, 9H), 1.96-2.01 (m, 3H), 2.97-3.02 (s, 6H), 3.12-3.17 (m, 1H), 3.34-3.38 (m, 1H), 3.48-3.56 (m, 2H), 3.77 (m, 1H) 4.11 (m, 4H). MS m/z: 471.7 (M+1) 21

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-methoxyacetamido)ethyl)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.27-1.29 (d, 3H), 1.96-1.97 (m, 1H), 2.35-2.6 (m, 2H), 3.00 (s, 3H), 3.07 (s, 3H), 3.30 (s, 3H) 3.4 (m, 1H), 3, 43-3.46 (d, 2H), 3.53 (m, 2H), 3.63 (m, 1H) 4.03 (d, 1H), 4.15-4.17 (d, 1H), 4.53 (d, 1H). MS m/z: 455 (M+1) 22

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(isopropoxycarbonylamino)ethyl)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.12-1.18 (m, 12H) 2.90 (d, 5H), 2.9 (s, 3H), 3.27 (d, 2H), 3.41 (d, 1H) 3.49 (m, 1H), 3.88 (d, 1H), 4.05 (m, 2H), 4.63 (d, 1H), 4.70 (m, 1H). MS m/z: 469.1 (M+1) 23

(4R,5S,6S)-4-Methyl-3-((3S,5S)-5-(4-methylpiperazin-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-(methylsulfamido )ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.10-1.12 (d, 3H), 1.21-1.23 (s, 3H), 1.75-1.81 (m, 1H), 2.39-2.50 (s, 3H), 2.84 (m, 4H), 2.88-3.03 (m, 4H), 3.22-3.30 (m, 3H) 3.39 -3.45(m, 3H), 3.45-3.48(m, 2H), 3.85-3.88(t, 2H), 4.10-4.45(d, 1H), 4 .50 (m, 1H). MS m/z: 516.1 (M+1) 24

(4R,5S,6S)-3-((3S,5S)-5-(4-Hydroxypiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(methylsulfamido )ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21-1.23 (d, 3H), 1.33-1.34 (d, 3H), 1.41-1.43 (m, 2H), 1.94-1.98 (m, 4H), 2.92-2.94 (dd, 2H), 3.01 (s, 3H), 3.24 (s, 3H) 3.34-3.36 (d, 2H), 3.41-3.42 (dd, 2H), 3.62-3.65 (dd, 4H), 4.12-4.14 (d, 1H). MS m/z: 517.2 (M+1) 25

(4R,5S,6S)-4-Methyl-3-((3S,5S)-5-(4-methylpiperazine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-6-((R)- 1-(trifluoromethylsulfamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.11-1.12 (d, 3H), 1.28-1.30 (d, 3H), 1.82 (m, 1H), 2.53 ( s, 3H), 2.85 (s, 3H), 3.25 (d, 1H), 3.50-3.32 (s, 3H) 3.8 (m, 3H), 3.92 (d, 2H), 4.06-4.08 (d, 4H), 4.38 (d, 1H). MS m/z: 568 (M-1). 26

(4R,5S,6R)-6-((R)-1-(2-Acetoxyacetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.09-1.11 (d, 3H), 1.22-1.24 (d, 3H), 1.84-1.88 (m, 1H), 2.10 (s, 3H), 2.91 (s, 3H), 2.97 (s, 3H), 2.98 (m, 1H) 3.24 (m, 2H), 3.34-3, 36 (m, 1H) 3.44-3.45 (d, 1H), 3.61-3.66 (m, 1H), 3.93-3.98 (m, 1H), 4.02-4 .04 (m, 1H), 4.29-4.33 (m, 1H), 4.52 (s, 2H). MS m/z: 483.1 (M+1). 27

(4R,5S,6S)-4-Methyl-6-((R)-1-(methylsulfamido)ethyl)-3-((3S,5S)-5-(morpholine-4-carbonyl)pyrrolidin-3-ylthio )-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.11-1.12 (d, 3H), 1.21-1.23 (d, 3H), 1.81-1.84 (m, 1H), 2.88 (m, 1H), 3.00-3.03 (d, 3H), 3.28 (d, 2H), 3.39-3.41 (d, 2H) 3.54 (m, 2H ), 3.67 (m, 3H), 3.85-3.90 (m, 4H), 4.11-4.12 (d, 1H) 4.59 (m, 2H). MS m/z: 503.1 (M+1). 28

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-ethoxy-2-oxoacetamido)ethyl)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.11-1.15 (d, 3H), 1.23-1.26 (d, 3H), 1.81 (m, 1H), 2.89 ( s, 3H), 2.96 (s, 3H), 3.25-3.29 (m, 3H), 3.49-3.51 (d, 2H) 3.60-3.62 (d, 1H ), 3.68-3.71 (m, 1H), 3.89-3.90 (m, 1H), 4.04-4.06 (m, 1H), 4.25-4.27 (m , 2H), 4.31-4.35 (d, 3H). MS m/z: 483.2 (M+1). 29

(4R,5S,6S)-4-Methyl-3-((3S,5S)-5-(morpholine-4-carbonyl)pyrrolidin-3-ylthio)-7-oxo-6-((R)-1- (trifluoromethylsulfamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.09-1.11 (d, 3H), 1.20 (s, 3H), 1.81 (s, 1H), 2.87 (s, 1H) , 3.32 (m, 2H), 3.5 (m, 3H), 3.60 (s, 3H) 3.70-3.80 (s, 6H), 3.90 (m, 1H), 4 .10 (d, 1H), 4.30 (t, 1H) 4.40-4.50 (m, 1H). MS m/z: 555.1 (M-1). thirty

(4R,5S,6S)-3-((3S,5S)-5-(4-Hydroxypiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)- 1-(trifluoromethylsulfamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.30-1.32 (d, 3H), 1.42-1.45 (d, 3H), 1.79 (m, 2H), 1.81- 1.91 (m, 3H), 2.88-2.92 (t, 1H), 3.09-3.13 (t, 1H), 3.27-3.30 (d, 3H), 3. 50-3.54 (t, 2H), 3.64-3.67 (d, 2H) 3.91 (s, 1H), 4.01 (m, 3H), 4.10 (d, 1H), 4.40 (t, 1H) 4.42 (s, 1H). MS m/z: 571 (M+1). 31

(4R,5S,6R)-6-((R)-1-((S)-2-Amino-4-methylpentanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.01 (d, 9H), 1.1 (m, 1H), 1.30-1.31 (d, 3H), 1.32-1.35 ( m, 3H), 2.88 (s, 3H), 3.00 (s, 3H), 3.08-3.12 (d, 1H), 3.35-3.37 (m, 3H) 3, 59-3.60 (d, 1H), 3.74-3.80 (d, 2H), 3.86-3.89 (m, 1H), 4.14-4.17 (d, 1H) 4 .30-4.32 (d, 1H) 4.40-4.44 (m, 1H). MS m/z: 496.2 (M+1). 32

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4- methyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.09-1.1 (d, 3H), 1.25-1.27 (d, 3H), 1.98 (m, 1H), 2.89 ( s, 3H), 2.95 (s, 3H), 3.22-3.26 (d, 2H), 3.36-3.37 (d, 2H), 3.48-3.50 (dd, 1H), 3.61 (m, 1H) 3.91-3.93 (d, 1H), 4.07-4.08 (m, 1H), 4.35-4.37 (d, 1H) 6 .07-6.25 (m, 1H). MS m/z: 461.1 (M+1). 33

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(thiophene-2 -sulfamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.13 (d, 3H), 1.18 (d, 3H) 1.94 (m, 1H), 3.05 (m, 3H) 3.07 (s , 3H), 3.25(m, 2H), 3.44(m, 2H), 3.72(m, 1H), 3.90(m, 1H), 4.03(m, 2H), 4 .8 (m, 1H), 7.24 (t, 1H), 7.78 (d, 1H), 7.88 (d, 1H). MS m/z: 529 (M+1). 34

(4R,5S,6S)-3-((3S,5S)-5-((R)-3-Hydroxypyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-(trifluoromethylsulfamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.2 (d, 3H) 1.4 (s, 3H), 2.1 (m, 4H) 2.98 (m, 1H), 3.35 (q , 2H), 3.60 (m, 5H), 3.77 (m, 1H), 4.17 (d, 1H), 4.46 (m, 1H), 4.54 (m, 2H). MS m/z: 555 (M-1). 35

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S)-5-(thiomorpholine-4 -carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.35-1.37 (d, 3H), 1.83-1.85 (m, 1H), 1.91 (d, 1H), 2.69-2.76 (m, 4H), 2.9-2.94 (m, 1H), 3.31-3.36 (q, 2H), 3. 52 (d, 1H), 3.36 (d, 1H), 3.78-3.80 (m, 2H) 3.90-3.91 (d, 2H), 4.13-4.14 (d , 1H), 4.43 (t, 1H) 4.47 (t, 1H) 6.02-6.28 (t, 1H). MS m/z: 519.1 (M+1). 36

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(methoxycarbonothioylamino)ethyl)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21-1.29 (d, 6H), 1.99-2.06 (m, 1H), 3.01 (s, 6H), 3.08 ( s, 3H), 3.7(s, 3H), 3.36(d, 1H), 3.47-3.54(m, 2H), 3.77(d, 1H) 4.12(d, 2H). MS m/z: 457 (M+1). 37

(4R,5S,6R)-3-((3S,5S)-5-(4-Carboxypiperidine-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-(2,2-difluoroacetamido )ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07 (d, 3H), 1.35 (d, 3H), 1.74 (m, 3H), 2.07 (m, 4H), 2.55 (m, 1H), 2.91 (m, 1H), 3.24 (m, 1H), 3.35 (d, 1H), 3.44 (m, 1H), 3.58 (m, 1H) 3.66 (m, 1H), 3.81 (m, 2H), 4.02 (m. 1H), 4.17 (m, 1H) 4.32 (m, 1H), 4.47 (m, 1H), 6.02-6.28 (t, 1H). MS m/z: 545.2 (M+1). 38

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S)-5-((sulfamoylamino) methyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm-1.20-1.21 (d, 3H), 1.35-1.35 (d, 3H), 1.70-1.76 (m, 1H), 1.91 (s, 1H), 2.71-2.73 (m, 1H), 3.34-3.35 (t, 2H), 3.38-3.40 (d, 1H), 3. 39-3.40 (d, 1H), 3.41-3.43(m, 1H), 3.64-3.67 (d, 1H) 3.86-3.88 (m, 1H), 3 .90 (d, 1H), 4.14-4.16 (d, 1H), 4.43-4.46 (d, 1H) 4.45-4.46 (m, 1H). MS m/z: 498.1 (M+1). 39

iodide 1-(2-amino-2-oxoethyl)-4-((2S,4S)-4-((4R,5S,6S)-2-carboxy-4-methyl-6-((R)-1- (methylsulfamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-ylthio)pyrrolidin-2-carbonyl)-1-methylpiperazin-1-ium ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.35 (d, 3H), 1.38-1.40 (d, 3H), 1.88-1.93 (m, 1H), 2.93 -2.99 (m, 1H), 3.15 (s, 3H), 3.46 (d, 2H), 3.52 (s, 3H), 3.57-3.59 (d, 1H), 3.78-3.93(m, 4H), 3.99(d, 1H) 4.00-4.16(m, 4H), 4.18(s, 2H), 4.32-4.34 (d, 1H), 4.64-4.69 (d. 2H), 4.81 (m, 1H). MS m/z: 573.2. 40

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(3,3 ,3-trifluoropropanamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.08-1.1 (d, 3H), 1.28 (d, 3H) 1.82 (m, 1H), 2.88-2.89 (s , 2H), 2.97-3.01 (s, 3H), 3.1-3.34 (m, 3H), 3.30-3.33 (d, 2H), 3.43-3.45 (d, 1H), 3.56-3.59 (m, 1H), 3.90-3.92(d, 1H), 4.03-4.04 (d, 1H), 4.29-4 .31 (m, 1H), 4.62-4.66 (m. 2H). MS m/z: 493.1 (M+1). 41

(4R,5S,6R)-6-((R)-1-((2,2-Difluoropentoxy)carbonylamino)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio) -4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.08-1.1 (d, 3H), 1.28 (d, 3H) 1.82 (m, 1H), 2.88-2.89 (s , 2H), 2.97-3.01 (s, 3H), 3.1-3.34 (m, 3H), 3.30-3.33 (d, 2H), 3.43-3.45 (d, 1H), 3.56-3.59 (m, 1H), 3.90-3.92(d, 1H), 4.03-4.04 (d, 1H), 4.29-4 .31 (m, 1H), 4.62-4.66 (m. 2H). MS m/z: 491.1 (M+1). 42

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S)-5-(1-oxo thiomorpholine-4-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.12 (s, 3H) 1.26 (s, 3H), 2.97 (m, 6H), 3.25 (t, 1H), 3.35 ( d, 1H) 3.50 (d, 1H), 3.64 (m, 1H), 3.70 (d, 1H), 3.95 (m, 2H), 4.07 (m, 2H), 4 .36 (m, 2H), 4.8 (m, 1H), 6.06 (t, 1H). MS m/z: 535 (M+1). 43

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-(4-methylpiperazine-1-carbonyl )pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.16 (d, 3H), 1.27 (d, 3H) 2.55 (s, 3H), 2.90-2.99 (s, 3H), 3.01 (m, 2H) 3.31 (m, 2H), 3.54 (m, 3H), 3.64 (m, 4H), 3.90 (m, 2H), 4.07 (m, 1H), 4.37(m, 1H), 4.70(m, 1H), 5.92-6.19(t, 1H). MS m/z: 516.1 (M+1). 44

(4R,5S,6R)-6-((R)-1-(2-Aminoacetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.11-1.15 (d, 3H), 1.17-1.19 (d, 3H) 1.82-1.84 (m, 1H), 2 .89-2.92 (s, 3H), 2.98-3.01 (s, 3H), 3.23-3.25 (m, 2H), 3.48-3.50 (d, 1H) , 3.56-3.58(d, 1H), 3.61-3.68(m, 3H), 3.91-3.94(m, 1H), 4.04-4.06(d, 1H), 4.60-4.62 (m, 1H), 4.7-4.76 (m. 2H). MS m/z: 440.1 (M+1). 45

iodide 4-((2S,4S)-4-((4R,5S,6R)-2-Carboxy-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-en-3-ylthio)pyrrolidin-2-carbonyl)-1,1-dimethylpiperazin-1-ium ¹ H NMR (D ₂ O) δ ppm: 1.10 (d, 3H), 1.26 (d, 3H) 1.81 (d, 1H), 2.88 (m, 1H), 3.17 ( s, 6H), 3.27 (m, 2H), 3.47 (m, 6H), 3.83-3.88 (m, 5H), 4.06 (d, 1H), 4.32-4 .36(m, 1H), 4.58-4.70(m, 1H), 5.91-6.18(t, 1H). MS m/z: 530.2. 46

iodide 1-(2-amino-2-oxoethyl)-4-((2S,4S)-4-((4R,5S,6R)-2-carboxy-6-((R)-1-(2.2 -difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-ylthio)pyrrolidin-2-carbonyl)-1-methylpiperazin-1-ium ¹ H NMR (D ₂ O) δ ppm: 1.20 (d, 3H), 1.40 (d, 3H) 1.83 (m, 1H), 1.86 (m, 1H), 2.87- 2.93 (m, 1H), 3.25 (m, 1H), 3.27 (m, 1H), 3.45 (s, 3H), 3.58-3.60 (m, 1H), 3 .82-3.97 (m, 6H), 4.14-4.17 m, 2H), 4.30-4.33 (m, 1H), 4.47-4.51 (m, 2H), 4.64-4.69 (d. 2H), 4.81 (m, 1H) 6.03-6.29 (t, 1H). MS m/z: 573.2. 47

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-((2, 2,2-Trifluoropentoxy)carbonylamino)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H), 1.31 (d, 3H) 1.97 (m, 1H), 2.98 (s, 3H), 3.04 ( s, 3H), 3.34 (m, 1H), 3.43 (m, 1H), 3.53-3.54 (dd, 2H), 3.67-3.71 (m, 2H), 4 .03 (t, 1H), 4.12-4.18 (m, 2H), 4.56-4.62 (m, 2H). MS m/z: 509 (M+1) 48

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-formimidamidoethyl)-4-methyl-7-oxo-1 -azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.39 (d, 3H), 1.42-1.43 (d, 3H) 1.92-1.96 (m, 1H), 2.99 (s , 3H), 3.05 (s, 3H), 3.24-3.25 (d, 1H), 3.40-3.43 (d, 1H), 3.57-3.67 (m, 3H ), 3.97-4.05 (m, 2H), 4.58-4.59 (d, 1H), 4.61-4.68 (m, 1H), 8.81 (s, 1H). MS m/z: 410.1 (M+1). 49

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S)-5-(1,1 dioxothiomorpholine-4-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.21 (d, 3H), 1.32-1.37 (d, 3H) 1.96-1.98 (m, 1H), 3 .00 (m, 1H), 3.37 (dd, 6H), 3.53-3.60 (d, 2H), 4.03 (d, 4H), 4.15-4.17 (d, 2H ), 4.43-4.47(m, 2H), 6.02-6.29(m, 1H). MS m/z: 550.1. fifty

(4R,5S,6R)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-3-(6,7-dihydro-5H-pyrazolo[1,2-a][1,2 ,4]triazol-4-ium-6-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate ¹ H NMR (D ₂ O) δ ppm: 1.05-1.07 (s, 3H), 1.36-1.38 (d, 3H), 3.38 (t, 1H), 3.66 ( d, 1H), 4.24 (m, 2H), 4.47 (m, 2H), 4.91-4.94 (d, 1H), 5.07 (d, 2H), 6.02-6 .29 (m, 1H), 9.03 (d, 2H). MS m/z: 428.1 (M ⁺ ). 51

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-((S)-2-( methylsulfamido)propanamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H), 1.40 (d, 3H), 1.92 (s, 2H), 3.00 (s, 3H), 3.07 (m, 3H), 3.10 (m, 3H), 3.30-3.40 (m, 3H), 3.53-3.55 (d, 1H), 3.6 (m, 1H), 4.00-4.02 (m, 3H), 4.13-4.16 (d, 2H) 4.34-4.38 (m, 1H), 4.68 (m, 1H). MS m/z: 532.1 (M+1). 52

(4R,5S,6R)-4-Methyl-7-oxo-3-((3S,5S)-5-((sulfamoylamino)methyl)pyrrolidin-3-ylthio)-6-((R)-1-( (2,2,2-Trifluoropentoxy)carbonylamino)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.25 (d, 3H), 1.31 (d, 3H), 1.58-1.66 (m, 1H), 2.60-2.68 ( m, 1H), 3.22-3.26 (m, 1H), 3.41-3.46 (m, 3H), 3.50-3.52 (m, 2H), 3.71-3, 79 (m, 1H), 3.94 (t, 1H), 4.13-4.15 (m, 2H), 4.44-4.64 (m, 2H). MS m/z: 546.1 (M+1). 53

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-((Z)-2-(methoxyimino)propanamido) ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H), 1.36 (d, 3H), 2.97 (s, 3H), 3.02 (s, 3H), 3.07 -3.12 (s, 3H), 3.30-3.34 (m, 2H) 3.36 (m, 1H), 3.57 (m, 1H), 3.48-3.51 (m, 1H ) 3.80 (m, 1H), 4.00 (s, 3H), 4.15 (m, 2H) 4.53 (m. 1H) 4.68 (m, 1H) MS m/z: 482 ,1 (M+1). 54

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-((E)-2-(methoxyimino)propanamido) ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.30-1.32 (d, 3H), 1.42-1.44 (d, 3H), 2.64 (s, 3H), 2.84 ( m, 2H), 2.98 (s, 3H), 3.02 (s, 3H), 3.07 (s, 3H), 3.24 (m, 1H), 3.48-3.51 (m , 1H), 3.86 (m, 1H), 3.98 (m, 3H), 4.26 (m, 1H), 4.53 (m. 1H). MS m/z: 482.1 (M+1). 55

(4R,5S,6R)-6-((R)-1-(Carboxyformamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.16 (d, 3H) 1.29 (d, 3H), 1.41 (m, 1H) 2.00 (s, 2H), 2.99 (s , 3H), 3.06 (s, 3H), 3.42 (m, 2H), 3.75 (m, 2H), 3.90 (m, 1H), 4.06 (m, 1H), 4 .46 (m, 1H). MS m/z: 410 (M-CO ₂ ). 56

(4R,5S,6R)-6-((R)-1-((R)-2-Amino-3-hydroxypropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H) 1.32 (d, 3H), 1.41 (m, 1H) 2.69 (m, 1H), 2.99 (s , 3H), 3.07 (s, 3H), 3.34 (m, 2H), 3.55 (m, 1H), 3.72-4.14 (m, 5H), 4.15 (m, 1H), 4.47 (m, 1H) 4.68 (m, 1H). MS m/z: 468.1 (M-1). 57

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(N,N-dimethylsulfamoylamino)ethyl)-4- methyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19 (d, 3H), 1.30-1.32 (d, 3H) 2.70 (s, 6H) 2.87 (s, 3H), 2 .95 (s, 3H), 3.23 (m, 2H), 3.37 (m, 1H), 3.45 (m, 1H), 3.77 (m, 1H), 3.80 (m, 2H), 4.13(m, 1H), 4.40(m, 1H), 4.63(m, 1H). MS m/z: 490.1 (M+1). 58

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-((R) -tetrahydrofuran-2-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19 (d, 3H) 1.35 (d, 3H), 1.97 (m, 4H) 2.16 (m, 1H), 2.25 (m , 1H), 3.00 (s, 3H), 3.06 (s, 3H), 3.21 (d, 2H), 3.39 (m, 3H), 3.45 (m, 2H), 3 .70 (m, 2H), 3.90 (m, 2H). MS m/z: 481.1 (M+1). 59

(4R,5S,6R)-6-((R)-1-((R)-2-Aminopropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.09-1.11 (d, 3H) 1.19-1.20 (d, 3H), 1.38-1.42 (d, 3H), 1 .70 (m, 1H) 2.81 (d, 1H), 2.96 (s, 6H), 3.17-3.20 (d, 1H), 3.25-3.27 (m, 1H) , 3.35-3.36 (m, 1H), 3.45-3.46 (d, 1H), 3.83-3.87 (d, 1H), 4.03-4.06 (d, 1H), 4.33-4.35 (m, 1H). MS m/z: 454.2 (M+1). 60

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-hydroxyacetamido)ethyl)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H) 1.39-1.41 (d, 3H), 1.95-1.99 (m, 1H) 2, 97 (s, 3H), 3.06 (s, 3H), 3.39-3.47 (m, 2H), 3.68-3.73 (d, 1H), 3.94-3.96 ( d, 2H), 4.32-4.34(d, 1H), 4.46-4.51(m, 1H), 4.69(d, 1H). MS m/z: 441.1 (M+1). 61

(4R,5S,6R)-6-((R)-1-(2,2-Difluoropropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4- methyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.22 (d, 3H) 1.27 (d, 3H), 1.87 (s, 3H) 1.97 (m, 1H), 3.00 (s , 3H), 3.02 (m, 1H), 3.07 (s, 3H), 3.09 (m, 1H) 3.35 (m, 1H), 3.45 (m, 1H), 3, 60 (t, 1H), 4.02 (m, 1H), 4.16 (d, 1H), 4.42 (d, 1H), 4.47 (d, 1H). MS m/z: 475.1 (M+1). 62

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-formamidoethyl)-4-methyl-7-oxo-1 -azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.29 (d, 3H) 1.49 (d, 3H), 1.97-2.06 (m, 2H) 2.97 (s, 3H), 3 .04 (s, 3H), 3.45-3.49 (dd, 1H), 3.56 (m, 1H), 3.73-3.78 (m, 1H), 3.89 (m, 1H ), 3.91 (m, 1H), 4.04-4.08 (m, 1H), 4.50 (m, 1H), 4.83 (m, 1H), 8.75 (s, 1H) . MS m/z: 411.1 (M+1). 63

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-(ethylsulfonyl)acetamido)ethyl)-4 -methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19 (d, 3H) 1.39 (d, 3H), 1.92-1.98 (m, 1H) 2.92 (s, 3H), 3 .00 (s, 3H), 3.37 (m, 1H), 3.39-3.43 (dd, 2H), 3.46 (t, 1H), 3.67 (m, 1H), 3, 69-3.72(m, 1H), 4.04(m, 1H), 4.46-4.49(m, 1H), 4.81(m, 1H). MS m/z: 517.1 (M+1). 64

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(2,2 ,2-trifluoroacetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H) 1.41 (d, 3H), 2.98 (s, 3H), 3.05 (s, 3H), 3.12- 3.18 (m, 1H), 3.31 (d, 1H), 3.37-3.41 (m, 2H), 3.78 (m, 3H), 4.03 (d, 1H), 4 .10 (t, 1H), 4.53 (t, 1H), 7.33 (s, 1H), 8.11 (d, 1H) 8.25 (d, 1H). MS m/z: 479.1 (M+1). 65

(4R,5S,6R)-6-((R)-1-(2,2-Difluoro-2-(thiophen-2-yl)acetamido)ethyl)-3-((3S,5S)-5-( dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H) 1.41 (d, 3H), 2.98 (s, 3H), 3.05 (s, 3H), 3.12- 3.18 (m, 1H), 3.31 (d, 1H), 3.37-3.41 (m, 2H), 3.78 (m, 3H), 4.03 (d, 1H), 4 .10 (t, 1H), 4.53 (t, 1H), 7.33 (s, 1H), 8.11 (d, 1H) 8.25 (d, 1H). MS m/z: 543 (M+1). 66

(4R,5S,6R)-6-((R)-1-(2-(Dimethylamino)-2-oxoacetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio )-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.22 (d, 3H) 1.34-1.36 (d, 3H), 1.94-1.99 (m, 1H) 2, 98-3.00 (s, 6H), 3.10 (s, 6H), 3.35-3.40 (m, 1H), 3.40-3.47 (dd, 1H), 3.610-3, 63 (d, 1H), 3.72-3.77 (dd, 1H), 4.01-4.06 (m, 1H), 4.18-4.21 (m, 1H), 4.47- 4.50 (m, 1H). MS m/z: 482.1 (M+1). 67

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-((S)-2-hydroxy-4-methylpentanamido )ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.26 (d, 6H) 1.33 (d, 3H), 1.39 (d, 3H), 1.56 (m, 1H), 1.68 ( m, 2H), 2.94 (m, 1H), 2.98 (s, 3H), 3.05 (s, 3H), 3.19 (m, 1H), 3.48 (d, 1H), 3.57 (dd, 1H), 3.67 (m, 1H), 3.94-3.98 (m, 1H), 4.02 (m, 1H), 4.12-4.17 (m, 1H), 4.38 (t, 1H), 4.49-4.52 (dd, 1H), 5.10 (dd, 1H). MS m/z: 497 (M+1). 68

(4R,5S,6R)-6-((R)-1-((S)-2-Aminopropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (DMSO-d ₆ ) δ ppm ^: 1.12 (d, 3H) 1.19 (d, 3H), 1.39 (d, 3H), 1.70 (m, 1H) 2.8 ( s, 3H), 2.95 (s, 3H), 3.18-3.24 (dd, 3H), 3.38-3.43 (d, 3H), 3.6 (dd, 1H), 3 .82-3.87 (m, 4H), 4.02-4.03 (d, 1H), 4.28-4.32 (m, 1H), 4.43 (m, 1H) 4.6 ( e, 1H). MS m/z: 454.1 (M+1). 69

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(morpholine-4-carboxamido)ethyl )-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (DMSO-d ₆ ) δ ppm: 1.24 (d, 3H) 1.28-1.29 (d, 3H), 1.98 (m, 1H), 2.99 (s, 3H) 3.03 (s, 3H), 3.07-3.12 (dd, 2H), 3.35-3.40 (dd, 4H), 3.44-3.46 (d, 1H), 3. 70 (dd, 4H), 3.80-3.82 (d, 2H), 3.93-3.95 (d, 1H), 4.15-4.19 (m, 1H), 4.22- 4.26 (m, 2H). MS m/z: 496 (M+1). 70

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(methylsulfamido)acetamido) ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.15 (d, 3H) 1.29 (d, 3H), 2.95 (s, 3H), 3.00 (s, 3H) 3.04 (s , 3H), 3.27 (m, 1H), 3.36 (m, 1H), 3.73 (m, 2H), 3.86 (s, 2H), 4.01 (m, 1H), 4 .07-4.11(m, 1H), 4.47(m, 2H), 4.61(m, 2H). MS m/z: 518.1 (M+1). 71

(4R,5S,6R)-6-((R)-1-((S)-2-Amino-3-phenylpropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.97 (d, 3H), 1.18 (d, 3H), 2.97 (s, 3H), 3.08 (s, 3H) 3.08- 3.13 (dd, 2H), 3.20-3.25 (dd, 2H), 3.25 (m, 2H), 3.39-3.44 (dd, 1H), 3.53 (m, 2H), 3.66-3.70(m, 2H), 4.06-4.13(m, 1H), 4.29(m, 1H), 7.23-7.42(m, 5H) . MS m/z: 530.2 (M+1). 72

(4R,5S,6R)-6-((R)-1-((R)-2-Amino-3-phenylpropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.08 (d, 3H) 1.26 (d, 3H), 2.95 (s, 3H), 3.03 (s, 3H), 3.08 (m, 2H), 3.11-3.13 (d, 2H), 3.16-3.20 (m, 2H), 3.21 (d, 1H), 3.40 (m, 2H), 3.51 (d, 2H), 4.21-4.22 (m, 1H), 4.54 (m, 1H), 7.23-7.42 (m, 5H). MS m/z: 530.2 (M+1). 73

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-isopropoxy-2-oxoacetamido)ethyl)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H) 1.34-1.35 (m, 9H), 1.94-1.98 (m, 1H), 3.00 (s , 3H), 3.06 (d, 3H), 3.32-3.34 (m, 2H), 3.36 (d, 2H), 3.60-3.62 (d, 1H), 3, 70-3.72(m, 1H), 4.03(m, 1H), 4.14-4.17(d, 1H), 4.42-4.22(m, 1H), 5.13- 5.16 (t, 1H). MS m/z: 495.1 (M+1). 74

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-methoxy-2-oxoacetamido)ethyl)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H) 1.36-1.38 (d, 3H), 1.93-2.0 (d, 1H), 3 .00 (s, 1H), 3.08 (s, 3H) 3.32-3.35 (q, 1H), 3.44-3.47 (q, 1H), 3.60-3.62 ( d, 1H), 3.72-3.76 (q, 1H), 3.90 (s, 3H), 4.01 (t, 1H), 4.15-4.17 (d, 1H), 4 .42-4.46 (t, 1H). MS m/z: 469.1 (M+1). 75

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(methylamino)-2 -oxoacetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.36-1.37 (d, 3H) 1.92-1.95 (m, 1H), 2 .84 (s, 3H), 3.03 (s, 3H), 3.32 (s, 3H), 3.33 (m, 2H), 3.41 (dd, 1H), 3.60-3, 62 (d, 1H), 3.68-3.71 (t, 1H), 4.02 (t, 1H), 4.13 (d, 1H), 4.39-4.41 (t, 1H) , 4.76-4.81 (d, 1H). MS m/z: 468.1 (M+1). 76

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(4,4-difluoropiperidine-1-carbonyl)pyrrolidine -3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.35-1.37 (d, 3H) 2.09-2.13 (m, 3H), 3 .02 (m, 1H), 3.35-3.37 (dd, 2H), 3.57-3.60 (d, 2H), 3.64-3.65 (d, 2H), 3.75 (d, 2H), 4.09 (m, 1H), 4.15-4.16 (d, 2H), 4.43-4.47 (m, 2H), 4.74 (m, 1H), 6.02-6.29 (m, 1H). MS m/z: 537.1 (M+1). 77

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((S)-3-hydroxypyrrolidine-1-carbonyl )pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.14-1.21 (d, 3H), 1.35-1.37 (d, 3H) 2.01-2.09 (m, 2H), 3 .01(m, 1H), 3.35(m, 3H), 3.42-3.46(t, 3H), 3.47-3.70(dd, 3H), 4.01(t, 1H ), 4.1-4.19 (d, 1H), 4.45-4.47 (t, 1H), 4.70-4.81 (q, 2H), 6.02-6.29 (t , 1H). MS m/z: 503.1 (M+1). 78

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(methylsulfonyl)acetamido) ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.1-1.19 (d, 3H) 1.41-1.43 (d, 3H), 3.00 (s, 3H), 3.08 (s , 3H), 3.25 (s, 2H), 3.33-3.35 (m, 2H), 3.41-3.46 (dd, 2H), 3.54-3.56 (d, 2H ), 4.01-4.04(t, 2H), 4.15-4.19(d, 2H), 3.22-4.26(m, 2H), 4.40-4.44(m , 1H). MS m/z: 503.1 (M+1). 79

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-((R)-2-fluoro-4-methylpentanamido )ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.27 (d, 3H) 1.33 (m, 3H), 1.65-1.74 (m, 6H), 2.99 (s, 3H), 3.09 (d, 3H), 3.31-3.42 (m, 2H), 3.55-3.56 (m, 2H), 3.62-3.63 (dd, 2H), 4, 01 (m, 2H), 4.06-4.13 (d, 2H), 4.41-4.44 (m, 2H), 4.68-4.70 (m, 2H). MS m/z: 499.2 (M+1). 80

iodide 1-(((4S)-4-((4R,5S,6R)-2-carboxy-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo -1-azabicyclo[3.2.0]hept-2-en-3-ylthio)pyrrolidin-2-yl)methyl)-1-methylpyrrolidinium ¹ H NMR (D ₂ O) δ ppm: 1.11 (d, 3H), 1.20-1.22 (d, 3H), 1.49 (m, 1H), 2.24 (m, 4H) , 2.72 (m, 1H), 3.04-3.17 (m, 2H), 3.30 (s, 3H), 3.38 (m, 2H), 3.56-3.61 (m , 5), 3.79 (m, 2H), 4.13-4.15 (m, 1H), 4.43-4.46 (m, 1H), 4.73 (m, 1H), 6, 02-6.29 (m, 1H). MS m/z: 487.2. 81

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-((3S)-5-(pyrrolidin-1-ylmethyl )pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H), 1.37 (d, 3H), 1.51 (d, 1H), 2.08 (d, 4H), 2.67 (t, 1H), 3.06-3.13 (d, 1H), 3.40 (m, 8H), 3.73 (d, 1H), 3.83 (d, 2H), 4.15 ( t, 1H), 4.17-4.54 (t, 1H), 6.02-6.29 (t, 1H). MS m/z: 473.2 (M+1). 82

(4R,5S,6R)-6-((1R)-1-(2-(Difluoromethylsulfinyl)acetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4 -methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.05-1.12 (d, 3H), 1.15 (d, 3H), 1.19 (d, 3H), 1.31 (d, 3H) , 1.96-1.99 (m, 2H), 2.94-3.07 (s, 1H), 3.27-3.29 (m, 1H), 3.31 (m, 1H), 3 .59-3.63 (d, 2H), 3.84-3.85 (d, 2H), 3.93-4.02 (d, 2H), 4.35 (m, 1H), 4.79 (m, 1H). MS m/z: 523.1 (M+1). 83

(4R,5S,6R)-6-((R)-1-(2,2-Difluoro-4-methylpentanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio )-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.96-0.98 (d, 6H), 1.19 (d, 3H), 1.38 (d, 3H), 1.90-1.92 ( d, 2H), 1.99 (m, 1H), 3.02-3.03 (s, 6H), 3.26-3.29 (m, 1H), 3.31 (d, 1H), 3 .57-3.59 (m, 2H), 4.00-4.06 (d, 2H), 4.14 (m, 2H), 4.65-4.67 (m, 1H), 4.80 -4.86 (d, 1H). MS m/z: 517.2 (M+1). 84

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((1R)-1-(2-fluoropropanamido)ethyl)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21-1.28 (d, 3H) 1.33-1.35 (d, 3H), 1.50-1.52 (d, 3H), 3 .00 (s, 3H), 3.07 (s, 3H), 3.39-3.42 (m, 2H), 3.56-3.58 (d, 2H), 3.65-3.66 (m, 2H), 4.00 (d, 2H), 4.14 (t, 2H), 4.42 (d, 1H). MS m/z: 457.2 (M+1). 85

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-(methylsulfamidomethyl)pyrrolidin-3-ylthio )-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.22 (d, 3H) 1.37 (d, 3H), 2.73 (m, 2H) 3.13 (s, 3H), 3.36 (m , 3H), 3.60 (m, 3H), 3.85 (d, 2H), 4.05 (d, 1H), 4.17 (t, 1H), 4.45 (d, 1H), 6 .02-6.29 (t, 1H). MS m/z: 497.1 (M+1). 86

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(2,2 ,2-trifluoroethylsulfamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21-1.25 (d, 3H) 1.30-1.32 (d, 3H), 2.73 (s, 3H), 3.13 (s , 3H), 3.34 (m, 4H), 3.60-3.61 (m, 2H), 3.97 (m, 2H), 4.16-4.17 (d, 2H), 4, 44-4.47 (t, 1H), 4.61-4.80 (d, 1H). 87

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(2,2 ,3,3,3-Pentafluoropropanamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.21 (d, 3H) 1.38-1.40 (d, 3H), 3.00-3.07 (s, 3H), 3 .35 (s, 3H), 3.35-3.42 (m, 2H), 3.60-3.62 (m, 2H), 4.06 (m, 2H), 4.16-4.18 (m, 2H), 4.48 (m, 1H), 4.71-4.80 (m, 1H). 88

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-(4-(pyridin-4-yl)thiazol-2 -ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.05-1.11 (d, 3H), 1.21 (d, 3H), 3.32-3.34 (d, 1H) 3.61-3 .63 (d, 2H), 4.21-4.23 (m, 1H), 4.43-4.45 (m, 1H), 5.98-6.25 (t, 1H), 7.86 (d, 1H), 8.22 (s, 1H), 8.6 (d, 1H). MS m/z: 481.2 (M+1). 89

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((3,3-dimethylureido)methyl)pyrrolidine- 3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ^oneH NMR (D₂O)δppm: 1.20-1.21 (d, 3H), 1.30-1.37 (d, 3H) 2.64 (m, 1H), 2.92 (s, 6H), 3.32 (dd , 2H), 3.46 (m, 1H), 3.58-3.59 (dd, 2H), 3.73-3.74 (d, 2H), 3.97 (m, 2H), 4, 13-4.16 (d, 2H), 4.43-4.47 (t, 1H), 6.02-6.29 (t, 1H). MS m/z: 490.2 (M+1). 90

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-(morpholinomethyl)pyrrolidin-3-ylthio )-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ^oneH NMR (D₂O)δppm: 1.27 (d, 3H), 1.35-1.37 (d, 3H) 2.57-2.69 (dd, 1H) 2.70-2.77 (dd, 2H), 2, 82-2.88 (m, 3H) 3.34-3.38 (dd, 3H), 3.58-3.60 (d, 2H), 3.63-3.64 (m, 2H), 3 .77 (m, 4H), 4.14 (d, 2H), 4.42 (t, 1H), 6.02-6.29 (t, 1H). MS m/z: 489.2 (M+1). 91

(4R,5S,6R)-6-((R)-1-(2-(Dimethoxyphosphoryl)acetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4 -methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.22 (d, 3H) 1.32-1.41 (d, 3H), 2.66 (s, 2H) 3.00 (s, 3H), 3 .07 (s, 3H), 3.47 (d, 1H), 3.53 (m, 2H), 3.55-3.60 (d, 2H), 3.72 (s, 6H), 3. 81-3.84 (d, 2H), 4.16 (m, 2H), 4.36-4.38 (m, 1H). MS m/z: 533.1 (M+1). 92

(4R,5S,6R)-3-(2-Aminoethylthio)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3,2 ,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.07 (d, 3H), 1.27-1.29 (d, 3H), 2.93-2.94 (m, 1H), 3.11-3.14 (dd, 2H) 3.17-3.19 (dd, 1H), 3.59-3.60 (d, 1H) 4.13-4.16 (m, 1H), 4.43-4.47 (t, 1H) 6.02-6.29 (t, 1H). MS m/z: 364.1 (M+1). 93

(4R,5S,6R)-3-(2-(tert-Butoxycarbonylamino)ethylthio)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1- azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.00-1.02 (d, 3H), 1.19-1.22 (d, 3H), 1.36 (d, 9H), 2.67 ( d, 1H), 3.03-3.06 (m, 2H) 3.24 (m, 1H), 3.77-3.80 (d, 1H) 4.16-4.18 (t, 1H) , 6.08-6.35 (t, 1H) 7.12-7.13 (d, 1H), 8.90-8.92 (d, 1H). MS m/z: 462 (M-1). 94

4-(2-((4R,5S,6R)-2-carboxy-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[] iodide 3,2,0]hept-2-en-3-ylthio)thiazol-4-yl)-1-methylpyridinium ¹ H NMR (D ₂ O) δ ppm: 1.09-1.19 (d, 3H), 1.33-1.35 (d, 3H), 3.63-3.64 (m, 1H) 3 .64-3.65 (d, 1H), 4.22-4.23 (m, 1H), 4.25 (s, 3H), 4.36 (d, 1H), 5.98-6.11 (t, 1H), 8.37-8.39 (dd, 2H), 8.6 (d, 1H), 8.75-8.77 (dd, 2H). MS m/z: 495.1.

Example 95: (4 R ,5 S .6 R )-3-((3 R ,5 S )-5-(( R )-3-aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-(( S )-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid

Stage 1: (four R ,5 R .6 R )-4-nitrobenzyl 3-(diphenoxyphosphoryloxy)-4-methyl-6-(( R )-1-(2-(methyl((4-nitrobenzyloxy)carbonyl)amino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate

Rhodium octanoate (0.1 g, 0.128 mmol) was added to a solution of (R)-4-nitrobenzyl 2-diazo-4-((2R,3R)-3-((R)-1-(2-(methyl(( 4-nitrobenzyloxy)carbonyl)amino)acetamido)ethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate (3 g, 4.69 mmol) in acetone (60 ml) and refluxed for 1.5 hours. The reaction mixture was cooled to -50--40°C and diphenyl chlorophosphate (1.64 g, 6.1 mmol), diisopropylethylamine (1.1 ml, 6.71 mmol) and dimethylaminopyridine (0.05 g, 0.41 mmol) were added successively. mmol) and continued stirring for 1 hour at -10°C. The reaction mixture was treated with 0.5 M phosphate buffer (pH 7.4) and extracted with ethyl acetate (150 ml). The organic layer was separated and washed with water and brine. After drying over sodium sulfate, the organic layer was evaporated to give an oily product. The crude product, after purification by column chromatography, gave the title compound as a pale yellow solid. (2 g, 49.6%).

Stage 2: (4 R ,5 S .6 R )-4-nitrobenzyl 4-methyl-6-(( R )-1-(2-(methyl((4-nitrobenzyloxy)carbonyl)amino)acetamido)ethyl)-3-((3 S ,5 S )-1-((4-nitrobenzyloxy)carbonyl)-5-(( R )-3-((4-nitrobenzyloxy)carbonylamino)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate

Chilled solution (0 °C) (4R,5R,6R)-4-nitrobenzyl 3-(diphenoxyphosphoryloxy)-4-methyl-6-((R)-1-(2-(methyl((4-nitrobenzyloxy)carbonyl) amino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (5 g, 8.72 mmol) and (2S,4R)-4-nitrobenzyl4- mercapto-2-((R)-3-((4-nitrobenzyloxy)carbonylamino)pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate (7.5 g, 8.72 mmol) in acetonitrile was degassed using nitrogen for 10 minutes and N,N-diisopropylethylamine (2.2 ml, 13.3 mmol) was added and degassed using nitrogen for an additional 10 minutes. The reaction mixture was stirred for 3 hours at 0°C under nitrogen. The reaction mixture was treated with 0.5 M phosphate buffer (pH 7.4) and extracted with EtOAc (150 ml). The organic layer was separated and washed with water and brine. After drying over sodium sulfate, the organic layer was evaporated to give an oily product. The crude product after purification by column chromatography (15-17% methanol in dichloromethane) gave the title compound as an off-white solid residue. (6.2 g, 60%)

Step 3: (4R,5S,6R)-3-((3R,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-(( R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid

(4R,5S,6R)-4-nitrobenzyl4-methyl-6-((R)-1-(2-(methyl((4-nitrobenzyloxy)carbonyl)amino)acetamido)ethyl)-3-((3S,5S )-1-(4-nitrobenzyloxy)carbonyl)-5-((R)-3-((4-nitrobenzyloxy)carbonylamino)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[ 3,2,0]hept-2-ene-2-carboxylate (0.5 g) in 20 ml of a mixture of tetrahydrofuran: water (2:1) and a suspension of Pd/C (2 g) was hydrogenated for 1.5 hours. The reaction mixture was filtered through celite and washed with 30 ml of tetrahydrofuran:water (2:1). The filtrate was washed with EtOAc (30 ml x 6). The aqueous layer was treated with activated carbon (1 g) and filtered. The filtrate was lyophilized to give the title compound (0.1 g, 50%). ¹ H NMR (D ₂ O) -1.07-1.08 (d, 3H), 1.20-1.29 (d, 3H), 1.92 (m, 1H), 2.12 (m, 2H), 2.46 (m, 2H), 2.76 (s, 3H), 2.92 (m, 1H), 3.34-3.38 (m, 2H), 3.40 (d, 3H ), 3.60-3.64 (d, 2H), 3.76-3.78 (d, 3H), 3.93-3.96 (m, 1H), 4.02 (m, 1H), 4.48 (m, 1H). MS m/z: 493.6 (M-1).

Examples 96, 97, 100-135, 137-145, 147-166, 168-176, 178-186, 188-200, 202, 205-206, 209-231, 235-238, 241-273, 275-292 , 294-297, 299-312, 314-318, 320-325, 329-361 and 363-368 were prepared by treating the compound of formula (10) with the appropriate R ^A COOH according to the method of Preparations 12, 16 and 17, followed by the method indicated in example 1.

Examples 136, 201, 203, 204, 239, 240 and 362 were prepared following the method presented in Preparation 13.

Example 187 was prepared following the method presented in Preparation 19.

Examples 98 and 99 were prepared following the method described in Preparation 23.

Examples 146, 167, 177, 207, 208, 232-234 were prepared following the method described in Preparation 20 using the appropriate alkynes (see Scheme 2a).

Example 274 and 293 were prepared following the method presented in Preparation 24.

Example Structure Analytical data 96

(4R,5S,6R)-6-((R)-1-(2,2-Дифторацетамидо)этил)-4-метил-7-оксо-3-(пиридин-3-илметилтио)-1-азабицикло[3,2,0]гепт-2-ен-2-карбоновая кислота

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-(pyridin-3-ylmethylthio)-1-azabicyclo[3 ,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.15 (d, 3H), 1.34 (d, 3H), 3.30 (t, 1H), 3.54 (d, 1H), 4.02 (m, 2H), 4.19 (m, 2H), 6.14 (t, 1H), 7.46 (t, 1H), 7.92 (d, 1H), 8.52 (d, 2H) . MS m/z: 412.4 (M+1) 97

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-(pyridin-4-ylmethylthio)-1-azabicyclo[3 ,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.15 (d, 3H), 1.34 (d, 3H), 3.26 (t, 1H), 3.54 (d, 1H), 3.95 (d, 1H), 4.02 (d, 1H), 4.18 (d, 1H), 4.40 (t, 1H), 6.14 (t, 1H), 7.47 (d, 2H) , 8.47 (d, 2H). MS m/z: 412.4 (M+1) 98

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-methoxy-2-oxoethylamino)ethyl)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.24 (d, 3H), 1.29 (d, 3H), 1.96 (m, 2H), 2.99 (d, 3H), 3.07 (s, 3H), 3.37 (m, 3H), 3.48 (d, 2H), 3.54 (d, 1H), 4.06 (m, 2H), 4.24 (m, 2H) , 4.26 (m, 3H). MS m/z: 469.5 (M+1) 99

(4R,5S,6R)-6-((R)-1-(Carboxymethylamino)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.52 (t, 3H), 1.53 (t, 3H), 1.98 (m, 2H), 3.07 (d, 3H), 3.08 (d, 3H), 3.4-3.5 (m, 2H), 3.5 (m, 1H), 3.55 (d, 2H), 3.72 (d, 1H), 3.79 ( m, 1H), 4.65 (m, 1H), 4.29 (d, 2H). MS m/z: 439 (M-1) 100

(4R,5S,6R)-6-((R)-1-(2-(Dimethylamino)acetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4 -methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.71 (t, 3H), 1.75 (t, 3H), 1.92 (t, 1H), 2.29 (s, 1H), 2.80 -2.89 (m, 6H), 2.98 (d, 2H), 3.07 (s, 3H), 3.09 (d, 3H), 3.20 (d, 1H), 3.58 ( d, 1H), 3.72 (d, 1H), 4.16 (d, 2H), 4.36-4.39(d, 1H), 4.45 (t, 1H), 4.82 (t , 1H). MS m/z: 466.6 (M-1) 101

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-(methylcarbamoyl)pyrrolidin-3-ylthio )-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H), 1.37 (d, 3H), 2.08 (d, 1H), 2.81 (s, 3H), 2.90 (t, 1H), 3.36 (m, 2H), 3.60 (d, 1H), 3.71 (m, 1H), 3.99 (s, 1H), 4.17 (d, 1H) , 4.39-4.47 (dd, 2H), 6.16 (t, 1H): MS m/z: 447.5 (M+1) 102

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(2-(dimethylamino)ethylcarbamoyl)-pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.28 (d, 3H), 1.37 (d, 3H), 1.47 (s, 1H), 2.03 (t, 1H), 2.97 (d, 6H), 2.96 (t, 1H), 2.97 (t, 3H), 3.22 (d, 2H), 3.67 (d, 2H), 3.91 (m, 1H) , 4.16 (d, 2H), 4.45 (s, 1H), 6.16 (t, 1H). MS m/z: 504.6 (M+1) 103

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-Aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 ,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20 (d, 3H), 1.38 (d, 3H), 1.35 (d, 1H), 2.09-2.21 (dd, 1H) , 2.19-2.49 (dd, 1H), 2.81-2.87 (m, 1H), 3.18 (m, 1H), 3.36 (dd, 2H), 3.59 (d , 2H), 3.77 (m, 2H) 3.78-3.88 (m, 2H), 3.98 (m, 1H), 4.14-4.23 (m, 2H), 4.45 (t, 1H) 6.16 (t, 1H). MS m/z: 502.5 (M+1) 104

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(2-hydroxyethylcarbamoyl)pyrrolidin-3-ylthio)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.2 (d, 3H), 1.37 (d, 3H), 2.08 (d, 1H), 2.91 (m, 1H), 3.36 (d, 2H), 3.41 (s, 3H), 3.6 (d, 1H), 3.69 (s, 3H), 3.98 (s, 1H), 4.17 (d, 1H) , 4.44-4.47 (dd, 1H), 4.81 (t, 1H), 6.16 (t, 1H). MS m/z: 477.5 (M+1) 105

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(methoxycarbamoyl)pyrrolidin-3-ylthio)-4- methyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.24 (d, 3H), 1.35 (m, 1H), 1.49 (d, 3H), 2.37 (m, 1H), 2.85 (m, 1H), 3.36 (m, 1H), 3.58 (d, 1H), 3.60 (q, 1H), 3.76 (s, 3H), 3.96 (t, 1H) , 3.98 (d, 1H), 4.28 (t, 1H), 4.45 (t, 1H), 6.16 (t, 1H). MS m/z: 516.6 (M+1) 106

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-((S)-3-( methylamino)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.36 (d, 3H), 1.82 (d, 3H), 1.92 (s, 1H), 2.11 (s, 1H), 2.18 (d, 1H), 2.45-2.55 (m, 2H), 2.77 (s, 2H), 2.89 (d, 1H), 3.39 (m, 1H), 3.65 ( d, 3H), 3.74-3.79 (m, 4H), 4.45 (d, 2H), 4.75 (d, 1H), 4.81 (d, 1H) 6.16 (t, 1H). MS m/z: 515.58 (M+1) 107

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((S)-3-(dimethylamino)pyrrolidine- 1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H), 1.38 (3, 3H), 1.92 (m, 1H), 2.09 (m, 1H), 2.54 (m, 1H), 2.78 (s, 2H), 2.83 (s, 3H), 3.26 (dd, 1H), 3.59 (d, 2H), 3.75-3.82 ( m, 4H), 3.94-4.14 (m, 4H), 4.41 (d, 2H), 4.45-4.74 (m, 2H) 6.16 (t, 1H). MS m/z: 530.6 (M+1) 108

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)-1-(iminomethyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.23 (d, 3H), 1.47 (d, 3H), 2.99 (s, 3H), 3.02 (m, 1H), 3.10 (s, 3H), 3.36 (m, 1H), 3.37-3.53 (m, 2H), 3.59 (m, 1H), 4.00 (m, 1H), 4.09- 4.18 (m, 2H), 4.46 (m, 2H), 5.20 (m, 1H), 6.02 (t, 1H). MS m/z: 488.5 (M+1) 109

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-Aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -ethoxy-2-oxoacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07 (d, 3H), 1.24-1.34 (m, 6H), 1.85-1.92 (m, 2H), 2.15- 2.30 (m, 2H), 2.92 (m, 2H), 3.25 (m, 1H), 3.35 (m, 1H), 3.57 (m, 1H), 3.65 (m , 2H), 3.83 (d, 1H), 3.92 (d, 1H), 4.16 (m, 2H), 4.39 (m, 2H), 4.42-4.92 (m, 2H). MS m/z: 524.60 (M+1) 110

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-((S)-3-( methylsulfamido)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.32 (d, 3H), 1.38 (d, 3H), 1.92 (d, 1H), 2.00 (dd, 1H), 2.34 (m, 1H), 2.97 (m, 1H), 3.15 (s, 3H), 3.36 (s, 2H), 3.54 (m, 1H), 3.59 (d, 3H) , 3.86 (d, 1H), 3.97 (t, 1H), 4.17 (d, 1H), 4.43-4.80 (m, 2H), 4.80 (t, 2H), 6.16 (t, 1H). MS m/z: 580.64 (M+1) 111

(4R,5S,6R)-3-((3S,5S)-5-(3-(Benzyloxyamino)-3-oxopropylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2,2 -difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.27 (d, 3H), 1.33 (d, 3H), 2.36-2.43 (m, 2H), 2.82 (m, 1H) , 3.33(m, 1H), 3.39(m, 2H), 3.56-3.58(m, 2H), 3.71(m, 1H), 3.99(m, 1H), 4.13-4.16 (m, 2H), 4.39-4.46 (m, 2H), 4.91 (s, 2H), 6.02 (t, 1H) 7.47 (d, 2H ), 7.38-7.45 (m, 3H). MS m/z: 610.64 (M+1) 112

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(methylamino)acetamido) ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.22 (d, 3H), 1.26 (d, 3H), 1.87 (m, 1H), 2.76 (s, 3H), 2.99 (s, 3H), 3.09 (s, 3H), 3.59 (s, 2H), 3.78 (d, 3H), 3.85 (m, 2H), 3.99 (t, 1H) , 4.16 (d, 1H), 4.47 (t, 1H), 4.61 (t, 1H). MS m/z: 452.5 (M-1) 113

(4R,5S,6R)-6-((R)-1-((R)-2-Amino-4-methylpentanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.92-0.99 (m, 6H), 1.17 (d, 3H), 1.22 (d, 1H), 1.28 (d, 2H) , 1.69-1.80(m, 3H), 2.99(s, 3H), 3.07(s, 3H), 3.33(dd, 1H), 3.43(d, 2H), 3.52 (m, 2H), 3.54 (m, 2H), 4.14 (m, 2H), 4.57 (m, 2H). MS m/z: 496.64 (M+1) 114

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(3-(dimethylamino)-3-oxopropylcarbamoyl)pyrrolidine -3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.69 (d, 3H), 1.27 (d, 3H), 1.90-1.98 (m, 1H), 2.59 (d, 2H) , 2.82 (s, 4H), 2.96 (s, 3H), 3.36-3.48 (m, 3H), 3.62 (m, 1H), 3.65 (m, 1H), 4.04 (m, 1H), 4.33 (m, 2H), 4.70 (m, 2H), 6.16 (t, 1H). MS m/z: 515.6 (M+1) 115

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(3-(methoxyamino)-3-oxopropylcarbamoyl)pyrrolidine -3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.12 (d, 3H), 1.92 (d, 3H), 2.22 (m, 1H), 2.23-2.69 (m, 2H) , 2.73 (m, 1H), 3.13-3.20 (s, 3H), 3.13-3.19 (m, 2H), 3.39-3.52 (s, 3H), 3 .79 (m, 1H), 3.82-3.96 (m, 2H), 4.21-4.61 (m, 2H), 6.14 (t, 1H). MS m/z: 534.6 (M+1) 116

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(3-(2-hydroxyethylamino)-3-oxopropylcarbamoyl )pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.08 (3, 3H), 1.12 (d, 3H), 2.51-2.54 (m, 2H), 2.82 (m, 2H) , 3.18 (d, 2H), 3.18-3.37 (m, 3H), 3.48-3.66 (m, 4H), 3.67 (m, 2H), 4.15 (d , 2H), 4.47 (m, 1H), 6.16 (t, 1H). MS m/z: 548.5 (M+1) 117

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((S)-3-(N,N- dimethylsulfamoyl-amino)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.22 (d, 3H), 1.27 (d, 3H), 1.92-1.98 (m, 2H), 2.09 (m, 1H) , 2.82 (s, 6H), 3.05 (d, 1H), 3.36 (m, 1H), 3.37-3.47 (m, 3H), 3.61 (d, 2H), 3.83 (m, 2H), 4.18 (d, 2H), 4.46 (m, 2H), 4.82 (d, 1H), 6.16 (t, 1H). MS m/z: 609.6 (M+1) 118

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((S)-3-(3,3- dimethylureido)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.38 (d, 3H), 1.47 (d, 3H), 1.89-1.99 (m, 2H), 1.99-2.29 ( m, 1H), 2.89 (d, 6H), 3.34-3.40 (m, 3H), 3.59-3.67 (dd, 4H), 3.75 (m, 2H), 3 .85 (d, 1H), 4.18 (d, 1H), 4.47 (m, 1H), 4.48 (m, 1H), 4.88 (m, 1H), 6.16 (t, 1H). MS m/z: 573.6 (M+1) 119

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(2-cyanoacetamido)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R) -1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H), 1.42 (d, 3H), 1.98 (m, 1H), 2.27-2.34 (dd, 1H) , 2.97 (m, 1H), 3.36-3.49 (m, 3H), 3.51 (d, 1H), 3.62-3.74 (m, 2H), 3.80 (m , 2H), 3.85 (m, 1H), 3.90 (m, 1H), 4.17 (d, 2H), 4.81 (m, 4H), 6.16 (t, 1H). MS m/z: 569.6 (M+1) 120

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S)-5-(piperazine-1 -carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06 (d, 3H), 1.22 (d, 3H), 1.80 (m, 1H), 2.71 (m, 1H), 2.89 (m, 1H), 3.25-3.36 (m, 5H), 3.44 (m, 1H), 3.58 (d, 1H), 3.64 (m, 1H), 3.84- 3.91 (m, 5H), 4.15 (d, 1H), 4.45 (d, 1H), 6.02 (t, 1H). MS m/z: 502.6 (M+1) 121

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(2-Aminoacetamido)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R) -1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.99 (d, 3H), 1.09 (d, 3H), 1.36 (d, 3H), 1.96 (dd, 1H), 2.21 (dd, 1H), 2.78 (d, 1H), 3.18 (m, 3H), 3.18-3.31 (m, 3H), 3.52 (t, 3H), 3.66 ( t, 1H), 4.21 (d, 1H), 4.52 (m, 2H), 6.05 (t, 1H). MS m/z: 559.60 (M+1) 122

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-Aminopiperidine-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-(2 ,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H), 1.31 (d, 3H), 1.36 (d, 2H), 1.73 (m, 1H), 1.93 (d, 1H), 2.2 (d, 1H), 3.17-3.22 (q, 2H), 3.31-3.36 (q, 2H), 3.39-3.47 (m , 2H), 3.59 (m, 1H), 3.72-4.15 (m, 2H), 4.16 (m, 1H), 4.18 (m, 1H), 4.44 (m, 1H), 4.47 (m, 2H), 6.16 (t, 1H). MS m/z: 516.6 (M+1) 123

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((S)-3-(methoxycarbonylamino)pyrrolidine- 1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H), 1.38 (3, 3H), 2.54 (m, 1H), 2.78 (s, 3H), 2.83 (s, 3H), 3.26 (dd, 1H), 3.59 (d, 2H), 3.75-3.82 (m, 3H), 3.94-4.14 (m, 4H), 4.41 (d, 1H), 4.41-4.74 (m, 2H) 6.16 (t, 1H). MS m/z: 560.6 (M+1) 124

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 ,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.32 (d, 3H), 1.38 (d, 3H), 1.99 (d, 2H), 2.09 (d, 1H), 2.19 (m, 1H), 3.05 (m, 1H), 3.36 (m, 1H), 3.44 (m, 1H), 3.48 (d, 1H), 3.66 (m, 1H) , 3.89-3.73 (m, 3H), 4.06 (m, 1H), 4.40 (d, 1H), 4.47 (m, 1H), 4.68 (m, 1H), 4.82 (m, 1H), 6.16 (t, 1H). MS m/z: 502.6 (M+1) 125

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-((R)-2-Amino-4-methylpentanamido)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio )-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.92-0.99 (m, 6H) 1.15 (d, 3H), 1.17 (d, 3H) 1.75 (m, 1H), 1 .77 (d, 2H), 1.91 (d, 3H), 2.04 (m, 1H), 2.23 (m, 2H), 2.85 (d, 2H), 3.19 (m, 2H), 3.36 (m, 2H), 3.57 (m, 1H), 3.75 (m, 1H), 4.14 (d, 2H), 4.44 (m, 2H), 6, 29 (t, 1H). MS m/z: 615.70 (M+1) 126

(4R,5S,6R)-3-((3S,5S)-5-((S)-2-(Aminomethyl)morpholine-4-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1 -(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (m, 3H), 1.35-1.37 (m, 3H), 1.82-1.84 (m, 1H), 2.85-2.88 (m, 2H), 3.07-3.13 (m, 2H), 3.24-3.27 (m, 1H), 3.32-3.33 (m, 3H ), 3.45 (m, 3H), 3.57-3.68 (m, 2H), 3.81-3.93 (m, 2H), 4.14-4.16 (m, 1H), 4.32-4.35 (m, 1H), 4.43-4.47 (m, 1H) 6.29 (t, 1H). MS m/z: 532.6 (M+1) 127

(4R,5S,6R)-3-((3S,5S)-5-((S)-2-(Aminomethyl)morpholine-4-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1 -(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.17-1.19 (m, 3H), 1.28-1.32 (m, 3H), 1.92 (m, 1H), 2.82 ( m, 2H), 3.07-3.12 (m, 2H), 3.21-3.27 (m, 2H), 3.34-3.44 (m, 3H), 3.57-3, 86 (m, 3H), 3.91 (m, 2H), 4.06-4.09 (m, 1H), 4.14-4.16 (m, 1H), 4.32-4.47 ( m, 2H) 6.29 (t, 1H). MS m/z: 532.6 (M+1) 128

(4R,5S,6R)-6-((R)-1-(2-cyanoacetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.21 (m, 3H), 1.30-1.31 (m, 3H), 1.95-2.01 (m, 1H), 3.00-3.33 (d, 6H), 3.35-3.37 (m, 2H), 3.45-3.48 (m, 1H), 3.56-3.58 (m, 2H ), 3.70-3.77(m, 3H), 4.04(m, 1H), 4.15-4.17(m, 1H), 4.36-4.39(m, 1H). MS m/z: 450.5 (M+1) 129

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.22 (m, 3H), 1.25-1.29 (m, 3H), 1.91 (m, 1H), 2.09 ( m, 1H), 2.23 (m, 1H), 2.47 (m, 2H), 2.75 (s, 3H), 3.19 (m, 1H), 3.39 (m, 2H), 3.58 (m, 3H), 3.6-3.87 (m, 4H), 4.03 (m, 1H), 4.13 (m, 1H), 4.25 (m, 1H), 4 .46 (m, 1H). MS m/z: 493.6 (M-1) 130

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S)-5-((S) -pyrrolidin-3-ylcarbamoyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.24 (m, 3H), 1.29-1.37 (m, 3H), 1.93 (m, 1H), 2.12- 2.19 (m, 2H), 2.39-2.40 (m, 1H), 2.87-2.89 (m, 1H), 3.33-3.49 (m, 3H), 3. 62-3.68 (m, 2H), 3.70-3.73 (m, 2H), 3.80 (m, 2H), 4.17-4.29 (m, 1H), 4.43- 4.51 (m, 2H) 6.02 (t, 1H). MS m/z: 502.6 (M+1) 131

(4R,5S,6R)-3-((3S,5S)-5-(3-Aminoazetidine-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-(2,2-difluoroacetamido )ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (m, 3H), 1.25-1.29 (m, 3H), 1.92 (m, 1H), 2.83 ( m, 2H), 3.27-3.34 (m, 2H), 3.53-3.59 (m, 2H) 3.93 (m, 2H), 4.07-4.47 (m, 5H ), 4.60-4.64 (m, 1H) 6.09 (t, 1H). MS m/z: 488.52 (M+1) 132

(4R,5S,6R)-3-((3S,5S)-5-(4-Aminopiperidin-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-(2,2-difluoroacetamido )ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21-1.22 (m, 3H), 1.30-1.37 (m, 3H), 1.57-1.63 (m, 3H), 1.92(m, 1H), 2.13-2.16(m, 2H), 2.81-2.92(m, 2H), 3.26-3.36(m, 3H), 3, 51-3.59 (m, 3H), 3.94 (m, 2H), 4.14-4.16 (m, 1H), 4.43-4.48 (m, 2H), 6.02- 6.29 (m, 1H). MS m/z: 516.6 (M+1) 133

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(2-Aminoethylsulfamido)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R) -1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.05-1.21 (m, 3H), 1.30-1.37 (m, 3H), 2.01 (m, 2H), 2.30- 2.34 (m, 2H), 2.98 (m, 2H), 3.35 (m, 2H), 3.47-3.49 (m, 2H), 3.60-3.62 (m, 2H), 3.74-3.76(m, 2H), 3.78(m, 2H), 3.94(m, 2H), 4.14-4.17(m, 2H), 4.43 -4.46 (m, 1H), 6.01 (t, 1H). MS m/z: 609.7 (M+1) 134

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-(methyl((S)-pyrrolidine -3-yl)carbamoyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (m, 3H), 1.32-1.37 (m, 3H), 1.92 (m, 1H), 2.19- 2.23 (m, 1H), 2.43-2.46 (m, 1H), 2.92 (m, 1H), 3.08-3.10 (s, 3H), 3.28-3, 37 (m, 3H), 3.50-3.68 (m, 6H), 3.96 (m, 1H), 4.14-4.17 (m, 1H), 4.43-4.47 ( m, 1H), 4.59-4.63 (m, 1H), 6.02-6.29 (t, 1H). MS m/z: 516.6 (M+1) 135

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-((S)-3-methylpiperazine -1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.21 (d, 3H), 1.35-1.37 (d, 6H), 1.82-1.84 (m, 1H), 2.96 (m, 1H), 3.15-3.57 (m, 6H), 3.59 (m, 1H), 3.84-3.91 (m, 5H) 4.14-4.17 (m, 1H), 4.20 (m, 1H), 4.42-4.47 (m, 1H), 6.02 (t, 1H). MS m/z: 516.6 (M+1) 136

(4R,5S,6S)-6-((R)-1-(2-Aminoethylsulfamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.32-1.37 (m, 3H), 1.37 (m, 3H), 2.56-2.62 (m, 1H), 2.99- 3.08 (m, 4H), 3.32 (m, 3H), 3.39-3.48 (m, 3H), 3.52-3.59 (m, 4H), 3.82-3, 98 (m, 1H), 4.05-4.25 (m, 3H), 4.55 (m, 1H). MS m/z: 490.61 (M+1) 137

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((5-methoxy-4-oxo-4H- pyran-2-yl)methylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.23-1.32 (m, 6H), 2.96-2.99 (m, 1H), 3.29-3.45 (m, 2H), 3.57-3.59 (m, 1H), 3.69-3.74 (m, 1H), 3.78 (s, 3H), 4.00-4.03 (m, 2H), 4, 13-4.16 (m, 1H), 4.38-4.49 (m, 4H), 6.02-6.29 (m, 1H), 6.51 (s, 1H), 8.08 ( s, 1H). MS m/z: 571.6 (M+1) 138

(4R,5S,6R)-6-((R)-1-(3-Amino-2,2-difluoropropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio )-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.22 (m, 3H), 1.29-1.32 (m, 3H), 2.96-3.00 (m, 4H), 3.07-3.11(m, 3H), 3.31-3.39(m, 4H), 3.60-3.66(m, 2H), 3.81(m, 1H), 4, 01 (m, 1H), 4.16-4.18 (m, 1H), 4.46-4.49 (m, 1H), 4.71-4.81 (m, 1H). MS m/z: 490.5 (M+1) 139

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(2-( propylamino)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.98-1.08 (m, 6H), 1.20-1.29 (m, 5H), 1.70-1.82 (m, 3H), 2.96-3.07 (m, 7H), 3.27-3.59 (m, 4H), 3.83-3.86 (m, 2H), 3.91-3.94 (m, 2H ), 4.13-4.15 (m, 1H), 4.46-4.47 (m, 1H). MS m/z: 480.6 (M-1) 140

(4R,5S,6R)-3-((3S,5S)-5-(bis(2-Hydroxyethyl)carbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2,2-difluoroacetamido )ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.27-1.30 (m, 3H), 1.35-1.37 (m, 3H), 3.08 (m, 2H), 3.35- 3.37 (m, 2H), 3.44-3.48 (m, 4H), 3.54 (m, 3H), 3.73-3.76 (m, 4H), 4.03 (m, 1H), 4.15-4.18 (m, 1H), 4.44-4.47 (m, 1H) 6.02 (t, 1H). MS m/z: 521.6 (M+1) 141

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-Amino-2-(methylcarbamoyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6- ((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.32-1.37 (m, 6H), 2.77-2.89 (m, 2H), 3.00 (s, 3H), 3.19- 3.23 (m, 4H), 3.33-3.37 (m, 2H), 3.57-3.59 (m, 2H), 3.77-3.90 (m, 2H), 4, 10-4.16 (m, 2H), 4.43-4.47 (m, 2H), 6.02-6.29 (t, 1H). MS m/z: 559.60 (M+1) 142

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-Amino-2-(dimethylcarbamoyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6- ((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.37 (m, 6H), 2.69-2.82 (m, 6H), 3.20-3.21 (m, 1H), 3.33-3.39 (m, 3H), 3.57-3.59 (m, 2H), 3.77-3.80 (m, 2H), 3.91-4.00 (m, 2H ), 4.07-4.16 (m, 3H), 4.30 (m, 1H), 4.43-4.47 (m, 1H), 4.74-4.89 (m, 1H), 6.02-6.29 (t, 1H). MS m/z: 573.6 (M+1) 143

(4R,5S,6R)-6-((R)-1-(2,2-Difluoro-3-hydroxypropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio )-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.13-1.33 (m, 6H), 3.00-3.07 (d, 6H), 3.31-3.35 (m, 2H), 3.39-3.42 (m, 1H), 3.56-3.59 (m, 1H), 3.95-4.01 (m, 3H), 4.13-4.15 (m, 3H ), 4.46-4.50 (m, 1H), 4.71 (m, 1H). MS m/z: 491.5 (M+1) 144

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)-1-methylpyrrolidin-3-ylthio) -4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.46 (m, 6H), 2.08 (m, 1H), 2.84-2.87 (m, 3H), 2.95- 2.97 (m, 6H), 3.25-3.35 (m, 3H), 3.58-3.59 (m, 3H), 3.98 (m, 1H), 4.43-4, 47 (m, 2H), 6.02-6.29 (m, 1H). MS m/z: 475.6 (M+1) 145

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S)-5-(piperazine-1 -ylmethyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.32-1.37 (m, 6H), 1.58-1.61 (m, 1H), 2.65-2.89 (m, 6H), 3.27 (m, 4H), 3.30-3.37 (m, 2H), 3.49-3.60 (m, 2H), 3.77-3.96 (m, 2H), 4, 13-4.16 (m, 2H), 4.43-4.7 (m, 1H), 6.02-6.29 (m, 1H). MS m/z: 488.6 (M+1 ) 146

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(4-(hydroxymethyl)-1H-1,2 ,3-triazol-1-yl)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.12-1.14 (d, 3H), 1.67-1.87 (d, 3H), 2.90-3.05 (m, 3H), 3.11 (d, 3H), 3.22-3.26 (d, 1H), 3.38-3.39 (d, 1H), 3.96-3.98 (dd, 2H), 4, 12-4.14 (m, 2H), 4.15 (d, 1H), 4.74 (m, 4H), 5.25-5.29 (m, 1H), 7.21-7.23 ( e, 1H). MS m/z: 465.5 (M+1) 147

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(3-Amino-2,2-difluoropropanamido)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)- 6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21 (d, 3H), 1.33 (d, 3H), 2.09-2.11 (m, 2H), 2.33-2.37 ( m, 2H), 2.98 (m, 2H), 3.32-3.39 (d, 3H), 3.51-3.53 (d, 2H), 3.60-3.63 (d, 2H), 3.9-3.98 (m, 2H), 4.15-4.17 (d, 2H), 4.42-4.45 (d, 1H), 4.52-4.55 ( m, 1H), 6.02-6.29 (t, 1H). MS m/z: 609.6 (M+1) 148

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(Aminooxy)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1 -(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.05-1.07 (d, 3H), 1.25-1.37 (d, 3H), 1.92 (m, 2H), 3.1 ( m, 2H), 3.12-3.33 (m, 3H), 3.55-3.59 (m, 3H), 3.71-75 (d, 3H), 4.15-4.17 ( m, 2H), 4.81 (s, 2H), 6.02-6.29 (t, 1H). MS m/z: 518.6 (M+1) 149

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-((R)-3-( methylamino)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.03-1.07 (d, 3H), 1.20-1.21 (d, 3H), 1.92 (m, 1H), 2.01 ( d, 1H), 2.21 (m, 1H), 2.41-2.48 (m, 2H), 2.70-2.75 (m, 3H), 3.18-3.21 (d, 3H), 3.5-3.8 (m, 6H), 4.02-4.15 (d, 2H), 4.41 (d, 1H), 6.02-6.29 (t, 1H) . MS m/z: 516.6 (M+1) 150

(4R,5S,6R)-3-((3S,5S)-5-(((S)-3-Aminopyrrolidin-1-yl)methyl)pyrrolidin-3-ylthio)-6-((R)-1 -(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.07 (d, 3H), 1.22-1.28 (d, 3H), 2.32 (m, 1H), 2.46- 2.48 (d, 1H), 2.72-2.78 (m, 2H), 2.80-2.82 (d, 2H), 2.88-2.89 (d, 2H), 3, 32-3.33 (d, 2H), 3.35-3.37 (d, 2H), 3.58-3.60 (m, 2H), 3.87-3.88 (m, 2H), 4.14-4.17 (m, 1H), 4.45 (d, 2H), 6.02-6.29 (t, 1H). MS m/z: 488.5 (M+1) 151

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-((S)-3-( 2-(methylamino)acetamidooxy)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.05-1.07 (d, 3H), 1.20-1.22 (d, 3H), 2.23-2.25 (m, 2H), 2.47-2.50(m, 2H), 2.73-2.77(d, 2H), 2.98(m, 2H), 3.35-3.53(2, 3H), 3, 4-3.7 (m, 4H), 3.82 (m, 3H), 4.15-4.17 (m, 2H), 4.25 (d, 1H), 4.53 (m, 1H) , 6.02-6.29 (t, 1H). MS m/z: 589.6 (M+1) 152

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-(((S)-3- (methylamino)pyrrolidin-1-yl)methyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.07 (d, 3H), 1.22-1.28 (d, 3H), 2.32 (m, 1H), 2.46- 2.48 (m, 2H), 2.72-2.78 (m, 2H), 2.81-2.83 (d, 2H), 2.88-2.89 (m, 2H), 3. 31-3.32 (d, 2H), 3.33 (s, 3H), 3.35-3.37 (d, 2H), 3.57-3.59 (m, 1H), 3.87- 3.88 (m, 2H), 4.15-4.16 (m, 1H), 4.46 (d, 2H), 6.02-6.29 (t, 1H). MS m/z: 502.5 (M+1) 153

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(2-Amino-2-oxoethylamino)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6- ((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21-1.23 (d, 3H), 1.31-1.33 (d, 3H), 2.98 (m, 2H), 3.12 ( d, 2H), 3.33-3.34 (m, 4H), 3.51-3.53 (m, 4H), 3.82-3.84 (m, 3H), 4.35-4, 45 (d, 2H), 4.47 (m, 2H), 6.02-6.29 (t, 1H). MS m/z: 559.60 (M+1) 154

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-(2-Amino-2-oxoethylamino)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6- ((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.27-1.29 (d, 3H), 1.32-1.37 (d, 3H), 3.02 (d, 2H), 3.35- 3.43 (m, 6H), 3.51-3.52 (m, 3H), 3.81-3.82 (m, 4H), 4.01-4.15 (m, 2H), 4. 43-4.45 (m, 2H), 4.57 (d, 1H), 6.02-6.29 (t, 1H). MS m/z: 559.6 (M+1) 155

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-((R)-3-( 2-(methylamino)acetamido)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.02-1.07 (d, 3H), 1.20-1.28 (d, 3H), 2.23-2.27 (m, 2H), 2.82-3.14 (m, 4H), 3.15-3.17 (m, 5H), 3.61-3.62 (s, 3H), 3.81-3.83 (d, 4H ), 4.02 (d, 2H), 4.41 (d, 2H), 6.02-6.29 (t, 1H). MS m/z: 573.6 (M+1) 156

(4R,5S,6R)-6-((R)-1-(2-(2-Amino-2-oxoethylamino)acetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine- 3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.17-1.19 (d, 3H), 1.21-1.29 (d, 3H). 2.99-3.00 (m, 3H), 3.07-3.09 (d, 3H), 3.37-3.46 (m, 3H), 3.51-3.52 (m, 3H ), 3.81-3.82 (m, 2H), 4.01-4.15 (m, 2H), 4.43-4.45 (m, 2H), 4.57 (d, 1H), 6.02-6.29 (t, 1H). MS m/z: 495.6 (M-1) 157

(4R,5S,6R)-3-((3S,5S)-5-(4-Carbamimidoylpiperazine-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-(2,2-difluoroacetamido )ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.32-1.37 (d, 3H), 2.86 (m, 1H), 3.19- 3.22 (m, 2H), 3.32-3.37 (d, 3H), 3.46-3.57 (m, 5H), 3.61-3.62 (m, 4H), 3. 90 (m, 1H), 4.14-4.16 (m, 1H), 4.36-4.38 (m, 1H) 6.02 (t, 1H). MS m/z: 544.6 (M+1) 158

(4R,5S,6R)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-(4-(2-(methylamino )-acetyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.27 (d, 3H), 1.30-1.37 (d, 3H), 2.91 (s, 3H), 3.31- 3.33 (m, 2H), 3.54-3.56 (m, 3H), 3.5-3.57 (m, 4H), 3.63-3.68 (d, 4H), 3. 94 (d, 4H), 4.14-4.19 (m, 2H), 4.55 (m, 1H), 6.02-6.29 (t, 1H). MS m/z: 573.6 (M+1) 159

(4R,5S,6R)-3-((3S,5S)-5-(4-(2-Aminoacetyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-( 2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21-1.27 (d, 3H), 1.29-1.35 (d, 3H), 2.89-2.91 (m, 3H), 3.27-3.33 (d, 2H), 3.35-3.37 (d, 3H), 3.57-3.59 (d, 3H), 3.62-3.64 (d, 2H ), 3.70-3.71 (d, 2H), 3.92-3.98 (d, 2H), 4.05-4.06 (d, 1H), 4.14-4.16 (d , 1H), 4.75-4.81 (d, 2H), 6.02-6.29 (t, 1H). MS m/z: 559.60 (M+1) 160

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-(2-Aminoacetamido)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R) -1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.27-1.29 (d, 3H), 1.32-1.36 (d, 3H), 3.02 (m, 3H), 3.35- 3.43(m, 5H), 3.48-3.56(d, 3H), 3.82(m, 3H), 4.01-4.15(m, 2H), 4.18(m, 1H), 4.43-4.53 (m, 1H), 4.57-4.79 (m, 1H), 6.02-6.29 (t, 1H). MS m/z: 559.6 (M+1) 161

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-((S)-2-methylpiperazine -1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.07 (d, 3H), 1.21-1.25 (d, 3H), 3.13 (m, 2H), 3.33 ( m, 4H), 3.46 (m, 3H), 3.58-3.59 (m, 3H), 3.82 (m, 3H), 3.98 (m, 2H), 4.15-4 .17 (m, 1H), 4.43-4.47 (t, 2H), 6.02-6.29 (t, 1H). MS m/z: 516.6 (M+1) 162

(4R,5S,6R)-3-((3S,5S)-5-(1,4-Diazepan-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-(2,2 -difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.10 (d, 3H), 1.30-1.37 (d, 3H), 2.75 (d, 4H), 2.95 ( m, 1H), 3.01-3.11 (d, 3H), 3.30 (m, 4H), 3.60-3.62 (d, 3H), 3.72 (d, 1H), 3 .89-4.01 (m, 2H), 4.15-4.17 (d, 1H), 4.58 (m, 1H), 6.02-6.29 (t, 1H). MS m/z: 516.6 (M+1) 163

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-(methyl(2-(methylamino) ethyl)carbamoyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.07 (d, 3H), 1.30-1.37 (d, 3H), 2.20-2.21 (m, 2H), 3.01 (m, 1H), 3.33-3.39 (m, 6H), 3.55-3.58 (d, 2H), 3.60 (d, 1H), 3.78 (d, 2H), 3.78-3.82 (d, 2H), 4.15-4.17 (d, 2H), 4.15-4.17 (d, 1H), 4.43-4.47 ( t, 1H), 6.02-6.29 (t, 1H). MS m/z: 504.6 (M+1) 164

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-(Aminooxy)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1 -(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.05-1.07 (d, 3H), 1.30-1.37 (d, 3H), 2.02-2.14 (m, 2H), 3.04 (m, 1H), 3.33-3.35 (d, 1H), 3.37 (dd, 1H), 3.41-3.42 (d, 1H), 3.52-3, 58 (d, 4H), 3.72-3.74 (d, 2H), 4.02-4.04 (d, 1H), 4.15-4.18 (d, 1H), 4.43- 4.47 (m, 1H), 4.56-4.60 (m, 1H), 4.63-4.65 (m, 1H), 6.02-6.29 (t, 1H). MS m/z: 518.6 (M+1) 165

(4R,5S,6R)-6-((R)-1-(3-Aminopropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.02-1.05 (d, 3H), 1.08-1.11 (d, 3H), 2.81 (m, 3H), 3.01- 3.21 (s, 3H), 3.22-3.25 (d, 3H), 3.26-3.29 (d, 3H), 3.51-3.52 (m, 3H) 3.80 (d, 2H), 4.02-4.06 (m, 1H), 4.09-4.13 (m, 1H), 4.61 (d, 1H). MS m/z: 452.6 (M-1) 166

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(3-(methylamino)propanamido) ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.86-0.88 (m, 3H), 1.21-1.34 (d, 3H), 2.50-2.85 (s, 3H), 2.86-3.01 (s, 3H), 3.26-3.29 (m, 6H), 3.51-3.52 (m, 3H) 3.80 (m, 3H), 4.02 -4.07 (d, 2H), 4.09-4.13 (m, 1H), 4.49 (d, 1H) 4.61 (d, 1H). MS m/z: 466.6 (M-1) 167

(4R,5S,6S)-3-((3R,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(4 -(hydroxymethyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.9-0.95 (d, 3H), 1.01-1.19 (d, 6H), 1.92-2.60 (m, 5H), 3.24 (m, 1H), 3.34-3.36 (d, 2H), 3.63-3.68 (d, 3H), 3.70 (d, 1H), 3.96 (d, 2H), 4.96 (m, 2H), 7.21-7.23 (s, 1H). MS m/z: 506.6 (M+1) 168

(4R,5S,6R)-4-Methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-3-((3S,5S)-5-(piperazine- 1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.08 (d, 3H), 1.20-1.22 (d, 3H), 2.60-2.62 (m, 2H), 2.75-2.76 (d, 3H), 2.96 (m, 2H), 3.28-3.33 (m, 4H), 3.58-3.59 (d, 3H), 3, 81-3.88 (dd, 1H), 3.92 (m, 4H), 4.13 (m, 2H), 4.13-4.15 (d, 1H) 4.46 (d, 1H). MS m/z: 493.6 (M-1) 169

(4R,5S,6R)-4-Methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-3-((3S,5S)-5-((sulfamoylamino )methyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21-1.22 (d, 3H), 1.25-1.29 (d, 3H), 2.75 (s, 3H), 3.36- 3.38 (d, 3H), 3.38 (m, 2H), 3.50 (m, 2H), 3.61 (m, 2H), 3.87 (m, 2H), 4.52 (m , 2H) 4.63 (m, 1H). MS m/z: 489.6 (M-1) 170

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(Cyclopropylamino)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1 -(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.88 (m, 4H), 1.02 (m, 1H), 1.21-1.27 (d, 3H), 1.46 (d, 3H) , 2.44-2.66 (3H, m), 3.00-3.03 (m, 1H), 3.35-3.4 (d, 2H), 3.60-3.64 (d, 2H), 3.72-3.77 (d, 2H), 3.79 (d, 2H), 4.01-4.08 (d, 2H), 4.11-4.15 (d, 2H) , 4.43-4.47 (d, 1H), 6.02-6.29 (t, 1H). MS m/z: 542.6 (M+1) 171

(4R,5S,6R)-3-((3S,5S)-5-((Cyanomethyl)(2-(methylamino)ethyl)carbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-( 2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.07 (d, 3H), 1.21 (d, 3H), 2.76 (m, 4H), 3.03-3.09 ( t, 3H), 3.33-3.35 (d, 3H), 3.73 (m, 3H), 4.16-4.18 (d, 2H), 4.26 (d, 1H), 4 .30 (d, 2H), 6.02-6.29 (t, 1H). MS m/z: 529.6 (M+1) 172

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(((3S,5S)-5-(dimethylcarbamoyl )pyrrolidin-3-yl)(methyl)carbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.20 (d, 3H), 1.26-1.28 (d, 3H), 1.80-1.82 (m, 1H), 2.82 (s, 3H), 2.89 (s, 3H), 3.07 (s, 3H), 3.17 (d, 2H), 3.26 (d, 3H), 3.34-3 .35 (d, 3H), 3.57-3.59 (m, 3H), 4.14-4.16 (m, 2H), 4.45-4.63 (d, 2H), 6, 02-6.29 (t, 1H). MS m/z: 587.7 (M+1) 173

(4R,5S,6R)-3-((3S,5S)-5-((3-((S)-3-Aminopyrrolidin-1-yl)-3-oxopropyl)(methyl)carbamoyl)pyrrolidine-3- ylthio)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21-1.23 (d, 3H), 1.28-1.35 (d, 3H), 2.30 (m, 2H), 2.48 ( d, 2H), 2.64-2.66 (m, 2H), 2.77 (d, 2H), 2.96 (d, 2H), 3.09-3.27 (s, 3H), 3 .27 (m, 2H), 3.61 (m, 2H), 3.71 (m, 3H), 4.01 (d, 2H), 4.21 (d, 1H), 4.44 (d, 1H), 6.02-6.29 (t, 1H). MS m/z: 587.7 (M+1) 174

(4R,5S,6R)-3-((3S,5S)-5-((3-(1,4-Diazepan-1-yl)-3-oxopropyl)(methyl)carbamoyl)pyrrolidin-3-ylthio) -6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.05-1.07 (d, 3H), 1.20-1.37 (d, 6H), 2.75 (m, 3H), 2.95 ( m, 3H), 3.08 (m, 3H), 3.32-3.46 (m, 6H), 3.58-3.59 (d, 2H), 3.74-3.81 (d, 2H), 4.14 (d, 2H), 4.45 (m, 3H), 6.02-6.29 (t, 1H). MS m/z: 601.6 (M+1) 175

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(cyanomethylamino)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1 -(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.35-1.36 (d, 3H), 1.97-1.99 (m, 1H), 2.22-2.35(m, 2H), 3.02-3.15(m, 1H), 3.32-3.36(m, 1H), 3.44-3.48(m, 2H ), 3.58-3.70 (m, 3H), 3.73-3.78 (m, 2H), 3.81-3.88 (m, 2H), 4.04-4.06 (m , 1H), 4.14-4.15 (m, 2H), 4.43-4.44 (m, 1H), 4.67-4.81 (m, 1H), 6.01-6.28 (t, 1H). MS m/z: 541.6 (M+1) 176

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(4-(Aminomethyl)-1H-1,2,3-triazol-1-yl)pyrrolidin-1 -carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2 -en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.17-1.20 (d, 3H), 1.36-1.37 (d, 3H), 1.92 (m, 1H), 2.57- 2.74 (m, 3H), 3.11 (m, 2H), 3.31-3.46 (m, 2H), 3.58-3.59 (m, 1H), 3.72-3, 77 (m, 3H), 3.87 (m, 1H), 4.04-4.07 (m, 2H), 4.16 (m, 1H), 4.34 (m, 2H), 4.41 -4.45 (m, 1H), 5.44 (m, 1H), 6.02-6.29 (t, 1H). MS m/z: 583.6 (M+1) 177

(4R,5S,6S)-6-((R)-1-(4-(Aminomethyl)-1H-1,2,3-triazol-1-yl)ethyl)-3-((3R,5S)- 5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.01-1.03 (d, 3H), 1.67-1.69 (d, 3H), 1.75-1.77 (d, 1H), 1.92 (m, 2H), 2.99 (s, 3H), 3.09 (s, 3H), 3.35 (m, 3H), 3.75-3.78 (m, 2H), 3 .84-3.97(m, 2H), 4.35(s, 2H), 8.24(s, 1H). MS m/z: 464.6 (M+1) 178

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(4-(Aminomethyl)-1H-1,2,3-triazol-1-yl)pyrrolidin-1 -carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept- 2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.07 (d, 3H), 1.14-1.16 (d, 3H), 1.92 (m, 1H), 2.76 ( s, 3H), 2.96 (m, 2H), 3.11 (m, 2H), 3.38-3.40 (d, 3H), 3.40-3.41 (m, 2H), 3 .58-3.60 (m, 2H), 3.76-3.78 (d, 3H), 3.93-3.96 (m, 2H), 4.01-4.03 (m, 3H) , 4.25 (s, 2H). MS m/z: 574.6 (M-1) 179

(4R,5S,6R)-4-Methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-3-((3S,5S)-5-((R)-3- (methylamino)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.07 (d, 3H), 1.15-1.17 (d, 3H), 1.91 (m, 1H), 2.12 ( m, 1H), 2.43-2.47 (m, 2H), 2.48 (m, 2H), 2.99 (m, 1H), 3.02 (m, 1H), 3.13 (m , 3H), 3.45-3.47 (m, 4H), 3.58-3.60 (m, 2H), 3.76-3.78 (d, 3H), 3.93-3.96 (m, 2H), 4.02 (m, 2H), 4.34 (m, 1H). MS m/z: 507.6 (M-1) 180

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(dimethylamino)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.08-1.10 (d, 3H), 1.20-1.22 (d, 3H), 1.91 (m, 1H), 2.46 ( m, 2H), 2.81 (s, 6H), 2.92 (m, 1H), 3.59 (d, 2H), 3.34-3.38 (m, 2H), 3.40 (d , 3H), 3.60-3.64 (m, 2H), 3.71 (d, 1H), 3.82 (m, 3H), 4.01 (m, 1H), 4.46 (m, 1H). MS m/z: 507.6 (M-1) 181

(4R,5S,6R)-3-((3S,5S)-5-((4-(Aminomethyl)-1H-1,2,3-triazol-1-yl)methyl)pyrrolidin-3-ylthio)- 4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.18-1.19 (d, 3H), 1.20-1.21 (d, 3H), 1.27-1.29 (d, 2H), 1.91 (m, 1H), 2.23 (d, 1H), 2.73 (s, 3H), 3.05 (m, 2H), 3.22-3.26 (d, 2H), 3 .35 (d, 1H), 3.48-3.50 (dd, 1H), 3.76-3.78 (dd, 2H), 4.01 (m, 1H), 4.12 (s, 2H ), 4.35-4.37 (d, 1H) 4.63 (m, 1H). MS m/z: 491.6 (M-1) 182

(4R,5S,6R)-6-((R)-1-(2-(Dimethylamino)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S)-5-(piperazine- 1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.08 (d, 3H), 1.22-1.29 (d, 3H), 1.82-1.85 (m, 1H), 2.60-2.62 (m, 2H) 2.55 (m, 1H), 2.76 (s, 3H), 2.91-2.93 (m, 1H), 3.30 (s, 6H ), 3.47 (m, 1H), 3.76-3.78 (m, 8H), 4.21 (m, 1H), 4.44-4.52 (m, 2H). MS m/z: 507.6 (M-1) 183

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-Amino-2-(aminomethyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6- ((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07 (d, 3H), 1.32-1.35 (d, 3H), 1.91-1.95 (m, 2H), 2.46 ( m, 1H), 2.56 (m, 4H), 2.48 (m, 1H), 3.31 (m, 2H), 3.55 (d, 1H), 3.74-3.76 (m , 1H), 3.92 (m, 1H), 4.00-4.02 (m, 1H), 4.14-4.17 (d, 1H), 4.34-4.47 (m, 3H ), 6.02-6.29 (t, 1H). MS m/z: 531.6 (M+1) 184

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((S)-3-formimimidopyrrolidine-1-carbonyl )pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.07 (d, 3H), 1.32-1.35 (d, 3H), 2.16-2.27 (m, 1H), 2.95 (m, 1H), 2.81-2.87 (m, 2H), 3.18 (m, 2H), 3.35 (m, 2H), 3.58-3.60 (d, 3H), 3.71-3.72 (m, 3H), 4.15-4.17 (m, 2H), 4.42 (d, 2H), 6.02-6.29 (t, 1H) . MS m/z: 529.6 (M+1) 185

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-Amino-2-((methylamino)methyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio) -6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.11-1.16 (d, 3H), 1.32-1.35 (d, 3H), 1.79-1.80 (m, 2H), 2.46 (m, 2H), 2.75-2.76 (s, 3H), 2.86 (m, 2H), 3.23-3.26 (d, 3H), 3.34 (m, 1H), 3.56 (d, 1H), 3.73 (m, 1H), 3.92 (m, 1H) 4.06-4.07 (d, 1H), 4.15-4.17 ( d, 1H), 4.39-4.45 (m, 3H), 6.19 (t, 1H). MS m/z: 545.6 (M+1) 186

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6- ((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.21-1.26 (d, 3H), 1.30-1.32 (d, 3H), 1.79-1.80 (m, 2H) 2 .65-2.69 (m, 1H), 2.81-2.82 (m, 1H), 3.22-3.32 (d, 2H), 3.34 (m, 1H), 3.57 -3.59 (m, 3H), 3.90-3.92 (m, 1H), 4.06-4.08 (m, 3H), 4.15-4.17 (d, 1H) 4, 39-4.47 (dd, 3H), 6.19 (t, 1H). MS m/z: 532.6 (M+1) 187

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(isoxazol-3-yloxy)ethyl)-4- methyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.93-0.96 (d, 3H), 1.25-1.36 (d, 3H), 1.87-1.91 (m, 1H), 3.00 (s, 3H), 3.07 (s, 3H), 3.22-3.26 (d, 2H), 3.39-3.40 (m, 2H) 3.54-3.60 (d, 1H), 3.81 (d, 1H), 4.07-4.08 (m, 1H), 4.35 (d, 1H), 5.12 (m, 1H), 6.22 ( s, 1H), 8.39-8.45 (s, 1H). MS m/z: 451.5 (M+1) 188

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-4- methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.04-1.06 (d, 3H), 1.13-1.21 (d, 3H), 1.79-1.80 (m, 2H) 2 .46-2.51 (d, 1H), 2.65-2.69 (m, 1H), 2.73 (s, 3H), 2.81-2.82 (m, 1H) 3.06 ( m, 1H), 3.22-3.32 (d, 2H), 3.35 (d, 1H), 3.58-3.61 (m, 2H), 3.80-3.83 (d, 2H), 4.04-4.08 (d, 3H), 4.15-4.17 (d, 1H) 4.34-4.35 (m, 3H). MS m/z: 523.6 (M-1) 189

(4R,5S,6R)-3-((3S,5S)-5-(3-Aminoazetidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2 -(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.13-1.15 (d, 3H), 1.19-1.20 (d, 3H), 2.12-2.13 (m, 3H), 2.55-2.56 (m, 1H), 2.75-2.76 (s, 3H), 2.92-2.95 (m, 2H), 3.29-3.38 (d, 3H ), 3.54-3.58 (d, 2H), 3.83-3.85 (d, 2H), 3.87-3.89 (m, 1H), 4.01-4.05 (d , 1H), 4.41-4.45 (m, 1H), 4.51-4.52 (m, 1H). MS m/z: 479.6 (M-1) 190

(4R,5S,6R)-3-((3S,5S)-5-(4-Aminopiperidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2 -(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.13-1.15 (d, 3H), 1.19-1.21 (d, 3H), 1.60-1.63 (m, 2H), 2.13-2.17 (m, 3H), 2.55-2.57 (m, 2H), 2.76-2.77 (s, 3H), 2.93-2.95 (m, 3H ), 3.29-3.38 (m, 3H), 3.54-3.59 (d, 2H), 3.83-3.85 (d, 2H), 3.86-3.87 (m , 1H), 4.14-4.16 (d, 1H), 4.45-4.46 (m, 1H), 4.52-4.53 (d, 1H). MS m/z: 507.6 (M-1) 191

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-Amino-2-(aminomethyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-4- methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.03-1.06 (m, 3H), 1.17-1.25 (m, 3H), 1.89 (m, 1H), 2.46 ( m, 2H), 2.67-2.71 (m, 2H), 2.86 (d, 3H), 3.21-3.28 (m, 3H), 3.40-3.42 (m, 2H), 3.56 (d, 1H), 3.72-3.91 (m, 4H), 3.92 (m, 1H) 4.06-4.07 (d, 1H), 4.13- 4.28 (m, 2H), 4.41 (m, 1H). MS m/z: 522.6 (M-1) 192

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-Hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.22 (d, 3H), 1.28-1.29 (d, 3H), 1.81 (m, 1H), 2.09- 2.10 (m, 2H), 2.76 (s, 3H), 2.94 (m, 1H), 3.30 (m, 1H), 3.43-3.46 (m, 2H), 3 .50-3.55 (m, 3H), 3.65-3.69 (m, 3H), 3.72-3.76 (m, 2H), 3.94 (m, 1H), 4.13 -4.15(m, 1H), 4.45-4.48(m, 1H), 4.55-4.59(m, 1H). MS m/z: 494.6 (M-1) 193

(4R,5S,6R)-3-((3S,5S)-5-(4-(2-Aminoacetamido)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R) -1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.15-1.21 (m, 3H), 1.23-1.29 (m, 3H), 1.42-1.53 (m, 3H), 1.92 (m, 1H), 2.05-2.08 (m, 3H), 2.7 (s, 3H), 3.00-3.02 (m, 3H), 3.33-3, 37 (m, 3H), 3.61-3.65 (m, 2H), 3.77 (s, 2H), 3.81-3.82 (m, 2H), 4.01-4.14 ( m, 2H), 4.16-4.29 (m, 1H), 4.46-4.48 (m, 1H). MS m/z: 564.6 (M-1) 194

(4R,5S,6R)-3-((3S,5S)-5-((3S,4S)-3,4-diaminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)- 1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.13-1.22 (m, 3H), 1.26-1.28 (m, 3H), 1.92 (m, 1H), 3.00- 3.02 (m, 1H), 3.21-3.22 (m, 1H), 3.32-3.37 (m, 4H), 3.40-3.48 (m, 2H), 3. 88-3.90 (m, 3H), 4.03-4.16 (m, 2H), 4.29-4.45 (m, 2H) 6.19 (t, 1H). MS m/z: 517.6 (M+1) 195

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((S)-3-guanidinopyrrolidine-1-carbonyl )pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.29-1.31 (d, 3H), 1.35-1.37 (m, 3H), 1.92-1.95 (m, 1H), 3.02 (m, 1H), 3.35-3.43 (m, 3H), 3.58-3.60 (m, 3H), 3.68-3.70 (m, 2H), 3. 78-3.82 (m, 1H), 4.01 (m, 1H), 4.15-4.18 (m, 1H), 4.25-4.27 (m, 2H), 4.44- 4.59 (m, 2H) 6.19 (t, 1H). MS m/z: 544.6 (M+1) 196

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((S)-3-(2-guanidinoacetamido) pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.27-1.29 (d, 3H), 1.35-1.37 (m, 3H), 1.81 (m, 1H), 2.24- 2.25(m, 2H), 3.01-3.03(m, 2H), 3.35(m, 2H), 3.46(m, 2H), 3.69(m, 2H), 3 .77 (m, 2H), 3.84 (m, 2H), 4.08-4.17 (m, 1H), 4.44-4.47 (m, 2H), 4.60-4.63 (m, 1H) 6.19 (t, 1H). MS m/z: 601.6 (M+1) 197

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(cyclopropylamino)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.75 (d, 3H), 1.02-1.04 (m, 2H), 1.24-1.35 (d, 6H), 1.92 ( m, 2H), 2.00-2.11 (m, 2H), 2.24 (m, 2H), 2.46 (m, 2H), 2.54 (m, 1H), 3.38-3 .58 (d, 2H), 3.66 (d, 3H), 3.87-3.88 (m, 2H), 4.11-4.13 (m, 2H), 4.42 (d, 1H ). MS m/z: 519.6 (M-1) 198

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((3S,4S)-3,4-dihydroxypyrrolidine -1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.35-1.37 (d, 3H), 3.02-.3.06 (m, 1H) , 3.02-3.06 (m, 1H), 3.33-3.35 (m, 2H), 3.44-345 (dd, 2H), 3.60-3.62 (d, 2H) , 3.71-3.78 (m, 3H), 4.03-4.05 (m, 1H), 4.16-4.18 (d, 1H), 4.30-4.34 (m, 1H), 4.47(m, 1H), 4.65(m, 1H), 6.29(t, 1H). MS m/z: 519.5 (M+1) 199

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-Formimidamidopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.09 (d, 3H), 1.17-1.27 (d, 3H), 1.83 (m, 1H), 2.31 ( m, 1H), 2.57 (m, 2H), 2.76 (m, 3H), 2.96-2.98 (m, 2H), 3.32-3.25 (m, 2H), 3 .40-3.51 (m, 4H), 3.88-3.92 (m, 4H), 4.04 (m, 1H), 4.13-4.15 (m, 1H), 4.39 -4.48 (m, 2H). MS m/z: 520.6 (M-1) 200

(4R,5S,6R)-3-((3S,5S)-5-((3S,4S)-3,4-diaminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-( (R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.08 (d, 3H), 1.20-1.22 (d, 3H), 1.81-1.82 (m, 1H), 2.76 (m, 1H), 2.81 (m, 2H), 2.95 (m, 2H), 3.12-3.13 (d, 1H), 3.35-3.53 (m, 3H), 3.61 (d, 1H), 3.62-3.71 (m, 3H), 3.81-3.99 (m, 3H), 4.05 (d, 1H), 4.11 (d, 1H), 4.3-4.41 (m, 1H), 4.51 (m, 1H). MS m/z: 508.6 (M-1) 201

(4R,5S,6S)-3-((3S,5S)-5-((2-Aminoethyl)(2-hydroxyethyl)carbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(methylsulfamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.35-1.37 (d, 3H), 1.98 (m, 1H), 2.55- 2.57 (m, 1H), 2.88-2.89 (d, 1H), 3.14 (s, 3H), 3.20-3.26 (m, 2H), 3.31 (d, 3H), 3.49-3.50 (d, 4H), 3.59-3.78 (d, 3H), 3.88-3.90 (m, 1H), 3.96-3.99 ( m, 1H), 4.20-4.22 (m, 1H). MS m/z: 520.6 (M+1) 202

(4R,5S,6R)-3-((3S,5S)-5-((2-Aminoethyl)(2-hydroxyethyl)carbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.09 (d, 3H), 1.13-1.28 (d, 3H), 1.98 (m, 1H), 2.43- 2.44 (m, 2H), 2.81 (s, 3H), 2.95 (d, 2H), 3.08-3.1 (d, 3H), 3.21-3.26 (m, 2H), 3.76-3.79 (m, 3H), 3.82-3.87 (m, 3H), 3.97 (d, 3H), 4.13-4.15 (m, 1H) , 4.45 (m, 1H). MS m/z: 511.6 (M-1) 203

(4R,5S,6S)-4-Methyl-6-((R)-1-(methylsulfamido)ethyl)-7-oxo-3-((3S,5S)-5-((R)-3-( sulfamoylamino)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.23-1.25 (d, 3H), 1.34-1.39 (d, 3H), 2.08-2.12 (m, 2H), 2.31 (m, 2H), 2.55-2.57 (m, 1H), 2.98 (m, 1H), 3.11 (s, 3H), 3.14-3.18 (d, 2H), 3.20-3.26(m, 2H), 3.38-3.34(d, 2H), 3.78-3.80(m, 2H), 4.15(m, 1H) , 4.22 (m, 1H), 4.70-4.77 (m, 1H). MS m/z: 581.7 (M+1) 204

(4R,5S,6S)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-(trifluoromethylsulfamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.03-1.05 (d, 3H), 1.20-1.21 (d, 3H), 1.98 (m, 1H), 2.02- 2.03 (m, 1H), 2.43-2.45 (d, 1H), 2.92 (m, 1H), 3.17-3.18 (m, 1H), 3.35-3, 36 (m, 2H), 3.43-3.45 (m, 2H), 3.59-3.60 (m, 3H), 3.78-3.80 (m, 2H), 4.04- 4.15 (m, 1H), 4.17 (d, 1H), 4.49 (t, 1H). MS m/z: 556.6 (M+1) 205

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-((S)-pyrrolidine-2-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.15-1.20 (d, 3H), 1.29-1.30 (d, 3H), 1.75-1.78 (m, 1H), 2.21-2.22 (m, 3H), 2.46-2.48 (m, 2H), 2.85 (m, 1H), 3.20-3.22 (d, 1H), 3, 37-3.38 (m, 2H), 3.60 (m, 3H), 3.72-3.78 (m, 3H), 3.87-3.90 (m, 3H), 4.04- 4.08 (m, 2H), 4.13-4.16 (d, 1H), 4.35 (m, 1H), 4.44-4.46 (m, 1H). MS m/z: 519.6 (M-1) 206

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-((R)-pyrrolidine-2-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.15-1.20 (d, 3H), 1.29-1.30 (d, 3H), 1.75-1.78 (m, 1H), 2.21-2.22 (m, 3H), 2.46-2.48 (m, 2H), 2.85 (m, 1H), 3.20-3.22 (d, 1H), 3, 37-3.38 (m, 2H), 3.60 (m, 3H), 3.72-3.78 (m, 3H), 3.87-3.90 (m, 3H), 4.04- 4.08 (m, 2H), 4.13-4.16 (d, 1H), 4.35 (m, 1H), 4.44-4.46 (m, 1H). MS m/z: 519.6 (M-1) 207

(4R,5S,6S)-6-((R)-1-(4-(Fluoromethyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-methyl-7-oxo-3 -((3R,5S)-5-(piperazine-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.95-0.97 (d, 3H), 1.63-1.92 (m, 3H), 2.72 (m, 1H), 3.22- 3.24 (m, 6H), 3.60-3.64 (m, 2H), 3.82-3.85 (m, 8H), 4.02 (m, 1H), 8.31 (s, 1H), 5.31 (s, 1H), 5.6 (s, 1H). MS m/z: 508.6 (M+1) 208

(4R,5S,6S)-3-((3R,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(4-((methylamino)methyl )-1H-1,2,3-triazol-1-yl)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.95 (d, 3H), 1.72-1.76 (d, 3H), 1.98 (m, 1H), 2.72-2.76 ( d, 2H), 2.87 (s, 3H), 3.06-3.09 (s, 3H), 3.10 (s, 3H), 3.22-3.26 (d, 2H), 3 .36-3.37 (d, 2H), 3.48-3.50 (dd, 1H), 3.61 (m, 1H) 3.81 (m, 2H), 4.07-4.08 ( m, 1H) 4.39 (m, 1H). MS m/z: 478.6 (M+1) 209

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((R)-3-fluoropyrrolidine-1-carbonyl )pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.21 (d, 3H), 1.35-1.37 (d, 3H), 1.47 (s, 1H), 1.92- 2.10 (m, 3H), 2.34-2.4 (m, 1H), 3.00-3.07 (d, 2H), 3.33-3.41 (m, 2H), 3. 58-3.60 (m, 3H), 3.72-3.77 (m, 2H), 3.82-3.98 (m, 1H), 4.15-4.17 (m, 1H), 4.44-4.47 (m, 1H), 4.63 (m, 1H) 5.36-5.52 (m, 1H), 6.02-6.2 (t, 1H). MS m/z: 505 (M+1) 210

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((S)-3-fluoropyrrolidine-1-carbonyl )pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.21 (d, 3H), 1.36-1.37 (d, 3H), 1.48 (s, 1H), 1.92- 2.3 (m, 4H), 3.00-3.07 (d, 2H), 3.33-3.4 (m, 2H), 3.58-3.60 (m, 3H), 3. 72-3.77 (m, 2H), 3.82-3.98 (m, 1H), 4.15-4.17 (m, 1H), 4.44-4.47 (m, 1H), 4.63 (m, 1H), 5.36-5.52 (m, 1H), 6.02-6.29 (t, 1H). MS m/z: 505 (M+1) 211

(4R,5S,6R)-3-((3S,5S)-5-((3S,4S)-3-Amino-4-fluoropyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-6-((R )-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.21 (d, 3H), 1.29-1.30 (d, 3H), 1.98-2.00 (m, 2H), 2.56-2.89 (m, 4H), 3.31-3.59 (m, 6H), 3.94 (m, 2H), 4.16-4.31 (m, 2H), 4, 45-4.47 (m, 2H), 6.02-6.29 (t, 1H). MS m/z: 518 (M-1) 212

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-amino-2-((sulfamoylamino)methyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio) -6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.21 (d, 3H), 1.29-1.30 (d, 3H), 1.34-1.37 (m, 2H), 1.92 (m, 1H), 1.98-2.00 (m, 2H), 2.47-2.51 (m, 1H), 2.87-2.94 (m, 1H), 3, 27-3.35 (m, 3H), 3.49-3.59 (m, 3H), 3.87-3.94 (m, 1H), 4.14-4.16 (m, 1H), 4.31-4.45 (m, 1H), 4.45-4.47 (m, 2H), 6.02-6.29 (t, 1H). MS m/z: 610 (M+1) 213

(4R,5S,6R)-3-((3S,5S)-5-((3S,4R)-3-Amino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-6-((R )-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20 (d, 3H), 1.36-1.37 (d, 3H), 1.79 (m, 1H), 2.90 (m, 1H) , 3.30-3.35(m, 2H), 3.53-3.63(m, 3H), 3.71(m, 2H), 3.78-3.80(m, 3H), 3 .92 (m, 1H), 4.02-4.12 (m, 1H), 4.15-4.17 (m, 1H), 4.45 (m, 1H), 4.61 (m, 1H ). MS m/z: 516 (M-1) 214

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-Fluoropyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.09-1.12 (m, 3H), 1.28-1.34 (d, 3H), 2.47-2.49 (m, 2H), 2.76 (s, 3H), 2.99-3.09 (m, 1H), 3.30 (m, 1H), 3.35-3.39 (m, 1H), 3.43-3, 46 (m, 2H), 3.50-3.55 (m, 3H), 3.65-3.69 (m, 3H), 3.72-3.76 (m, 2H), 3.94 ( m, 1H), 4.12-4.14 (m, 1H), 4.16-4.18 (d, 1H) 4.45-4.48 (m, 1H), 4.55-4.59 (m, 1H). MS m/z: 498 (M+1) 215

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-Fluoropyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.05-1.07 (d, 3H), 1.30-1.31 (d, 3H), 2.43-2.45 (d, 2H), 2.76 (s, 3H), 2.99-3.09 (dd, 1H), 2.76 (s, 3H), 3.30 (m, 1H), 3.43-3.46 (m, 2H), 3.50-3.55(m, 3H), 3.58-3.63(m, 2H), 3.72-3.76(m, 2H), 4.14-4.16( m, 1H), 4.18-4.19 (m, 1H), 4.46-4.48 (m, 1H) 4.55-4.59 (m, 1H). MS m/z: 498 (M+1) 216

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-Amino-2-((sulfamoylamino)methyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio) -4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.22 (d, 3H), 1.32-1.34 (d, 3H), 1.98-2.00 (m, 2H) 2 .07-2.09 (m, 1H), 2.47-2.51 (m, 1H), 2.63-2.74 (m, 1H), 3.05-3.12 (m, 1H) , 3.32-3.35(m, 3H), 3.39-3.49(m, 2H), 3.53-3.55(m, 1H), 3.57-3.59(m, 1H), 3.74-3.78 (d, 1H), 3.81-3.90 (m, 4H), 4.07-4.15 (m, 1H), 4.23-4.29 ( m, 1H), 4.29-4.31 (m, 2H), 4.45-4.46 (d, 1H). MS m/z: 603 (M+1) 217

(4R,5S,6R)-3-((3S,5S)-5-((3S,4S)-3-Amino-4-fluoropyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6 -((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.08 (d, 3H), 1.22-1.29 (d, 3H), 2.02-2.05 (m, 1H), 2.03-2.04 (m, 1H), 2.75-.276 (d, 3H), 2.98-2.99 (m, 1H), 3.24-3.25 (m, 1H) , 3.32-3.41 (m, 3H), 3.52-3.56 (m, 1H), 3.73-3.82 (m, 2H), 3.87-3.93 (m, 4H), 4.13-4.15(m, 1H), 4.41-4.45(m, 1H), 4.46-4.48(m, 1H), 4.49-4.58( m, 1H). MS m/z: 512 (M+) 218

(4R,5S,6R)-3-((3S,5S)-5-((3S,4R)-3-Amino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6 -((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.8 (d, 3H), 1.25-1.27 (d, 3H), 1.79 (m, 1H), 2.7 ( s, 3H), 2.84 (m, 1H), 3.23 (d, 1H), 3.40-3.42 (m, 2H), 3.43-3.44 (m, 1H), 3 .52-3.58 (m, 1H), 3.7 (m, 2H), 3.79-3.81 (m, 5H), 4.02-4.12 (m, 1H), 4.13 -4.15(m, 1H), 4.4(m, 1H), 4.58(m, 1H). MS m/z: 510 (M+) 219

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(Aminomethyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1 -(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20 (d, 3H), 1.26 (d, 3H), 1.35 (m, 2H), 1.86 (m, 1H), 1.92 (m, 1H), 2.27 (m, 1H), 2.93 (m, 1H), 3.11 (m, 2H), 3.22 (m, 1H), 3.35 (m, 2H) , 3.45(m, 1H), 3.58(m, 2H), 3.67(m, 1H), 3.78(m, 2H), 3.9(m, 1H), 4.15( m, 1H), 4.45 (m, 2H), 6.15 (t, 1H). MS m/z: 515 (M+) 220

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(Aminomethyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-4-methyl-6-(( R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.22 (d, 3H), 1.28 (d, 3H), 1.29 (m, 1H), 1.35 (m, 2H), 1.86 (m, 1H), 1.92 (m, 1H), 2.0 (m, 1H), 2.27 (m, 1H), 1.69 (m, 2H), 2.93 (m, 1H) , 3.11 (m, 2H), 3.22 (m, 1H), 3.35 (m, 2H), 3.45 (m, 1H), 3.58 (m, 2H), 3.67 ( m, 1H), 3.78 (m, 2H), 3.9 (m, 1H), 4.15 (m, 1H), 4.45 (t, 2H), 6.15 (t, 1H). MS m/z: 508 (M+) 221

(4R,5S,6R)-3-((3S,5S)-5-(4-(2-Aminoethyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R) -1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.0 (d, 3H), 1.29 (d, 3H), 2.43-2.48 (m, 2H) 2.58-2.62 (m , 4H), 2.68-2.72 (m, 4H), 2.81-2.83 (m, 2H), 2.9 (m, 2H), 3.02 (m, 2H), 3, 17 (m, 2H), 3.39 (m, 2H), 3.64-3.69 (m, 2H), 3.8 (m, 2H) 3.93 (m, 3H). MS m/z: 538 (M+1) 222

iodide 1-(2-Aminoethyl)-4-((2S,4S)-4-((4R,5S,6R)-2-carboxy-4-methyl-6-((R)-1-(2-( methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-ylthio)pyrrolidin-2-carbonyl)-1-methylpiperazin-1-ium ¹ H NMR (D ₂ O) δ ppm: 1.04-1.08 (d, 3H), 1.18-1.20 (m, 3H), 2.47-2.53 (m, 2H), 2.73(m, 2H), 2.81-2.83(m, 1H), 3.02(m, 1H), 3.19-3.22(m, 6H), 3.64-3, 69 (m, 6H), 3.81 (m, 2H), 3.98 (m, 6H), 4.02-4.24 (m, 4H). MS m/z: 680 (M+1) 223

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-((2S,4S)-4-fluoropyrrolidine-2 -carboxamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.03-1.09 (d, 3H), 1.18-1.30 (d, 3H), 1.90 (m, 2H), 2.06- 2.08 (m, 1H), 2.46-2.51 (m, 2H), 2.99-3.00 (m, 4H), 3.07-3.11 (m, 3H), 3. 36-3.44(m, 4H), 3.61-3.67(m, 1H), 3.76(m, 1H), 4.15(m, 2H), 4.54(m, 2H) . MS m/z: 497 (M+) 224

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-((2S,4R)-4-hydroxypyrrolidine-2 -carboxamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.09 (d, 3H), 1.19-1.26 (d, 3H), 1.34 (m, 1H), 1.92 ( m, 4H), 2.15 (m, 2H), 2.47 (m, 2H), 2.99 (m, 4H), 3.07-3.09 (m, 3H), 3.35-3 .39 (m, 4H), 3.60 (m, 2H), 3.73-3.77 (m, 2H), 4.69 (m, 2H). MS m/z: 496 (M+1) 225

(4R,5S,6R)-4-Methyl-7-oxo-6-((R)-1-((S)-pyrrolidine-2-carboxamido)ethyl)-3-((3S,5S)-5- ((sulfamoylamino)methyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.22 (d, 3H), 1.29-1.30 (d, 3H), 1.72-1.75 (m, 2H), 1.92 ( m, 2H), 2.44-2.47 (m, 2H), 2.69-2.77 (m, 1H), 3.32-3.48 (m, 7H), 3.62-3, 67 (m, 2H), 3.4-3.76 (d, 1H), 3.85-3.86 (d, 1H), 4.02 (m, 1H), 4.14-4.16 ( m, 1H), 4.42-4.43 (m, 1H), 4.45 (m, 1H). MS m/z: 516 (M+) 226

(4R,5S,6R)-4-Methyl-7-oxo-6-((R)-1-((R)-pyrrolidine-2-carboxamido)ethyl)-3-((3S,5S)-5- ((sulfamoylamino)methyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.29-1.31 (d, 3H), 1.34 (d, 3H), 1.72-1.74 (m, 1H), 1.92 ( m, 2H), 2.07-2.08 (m, 2H), 2.46-2.47 (m, 1H), 2.73-2.76 (m, 1H), 3.32-3, 38 (m, 4H), 3.67-3.74 (m, 2H), 3.77 (m, 1H), 3.89-4.01 (m, 1H), 4.14 (m, 1H) , 4.15-4.17(m, 1H), 4.33-4.35(m, 1H), 4.44(m, 1H), 4.46-4.47(m, 1H), 4 .69-4.74 (m, 1H). MS m/z: 516 (M+) 227

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-((R) -pyrrolidine-2-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.08 (d, 3H), 1.22-1.26 (d, 3H), 1.86 (m, 1H), 1.91 ( m, 1H), 2.46 (m, 2H), 2.99 (m, 3H), 3.36 (m, 3H), 3.45 (m, 3H), 3.59 (m, 3H) 3 .74-3.77(m, 1H), 3.97(m, 1H), 4.15-4.17(m, 1H), 4.36(m, 2H), 4.46(m, 1H ), 4.61 (m, 1H). MS m/z: 480 (M+1) 228

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-((S) -pyrrolidine-2-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.22-1.25 (d, 3H), 1.31-1.34 (d, 3H), 1.89-1.92 (m, 1H), 2.06-2.08 (m, 2H), 2.45-2.46 (m, 2H), 2.99 (s, 3H), 3.07 (s, 3H), 3.36-3, 40 (m, 3H), 3.44-3.46 (m, 2H), 3.55-3.58 (m, 1H), 3.78-3.82 (m, 1H), 3.92- 3.98 (m, 1H), 4.14-4.16 (m, 1H), 4.33-4.35 (m, 1H), 4.42-4.44 (m, 1H), 4. 45-4.48 (m, 1H). mass 478 (M-1). MS m/z: 478 (M-1) 229

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(N-methylformimidamido)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.22 (d, 3H), 1.31-1.34 (d, 3H), 1.89-1.92 (m, 1H), 2.04-2.08 (m, 1H), 2.10-2.12 (m, 1H), 2.46-2.48 (m, 2H), 2.88-2.92 (m, 1H ), 3.07(s, 3H), 3.22-3.28(m, 2H), 3.32-3.40(m, 2H) 3.60-3.63(m, 2H), 3 .66-3.67 (m, 2H), 3.89-3.91 (m, 2H), 4.07-4.12 (m, 2H), 4.22-4.24 (m, 1H) , 4.45-4.48 (m, 1H). MS m/z: 522 (M+1) 230

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(1-methylguanidino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.22 (d, 3H), 1.27-1.29 (d, 3H), 1.89-1.92 (m, 1H), 2.01-2.03 (m, 1H), 2.08-2.12 (m, 1H), 2.48-2.52 (m, 2H), 2.82-2.89 (m, 1H ), 3.04 (s, 3H), 3.45-3.45 (m, 1H), 3.48-3.49 (m, 1H), 3.57-3.60 (m, 1H), 3.75-3.79 (m, 3H), 3.87-3.91 (m, 2H), 3.94-3.96 (m, 1H), 4.12-4.17 (m, 2H ), 4.38-4.44 (m, 1H) 3.43-4.46 (m, 1H). 231

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(1-methylguanidino) acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.22 (d, 3H), 1.27-1.29 (d, 3H), 1.80-1.83 (m, 1H), 2.02-2.03 (m, 1H), 2.44-2.46 (m, 1H), 2.95-2.96 (m, 1H), 2.99 (s, 3H), 3, 07 (s, 3H), 3.08-3.11 (m, 2H), 3.33-3.35 (m, 2H), 3.49-3.52 (m, 1H), 3.93- 3.97 (m, 1H), 4.14-4.18 (m, 3H), 4.45-4.47 (m, 2H). MS m/z: 496 (M+1) 232

(4R,5S,6S)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(4 -(methoxymethyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.24-1.26 (d, 3H), 1.66-1.68 (m, 1H) 1.76-1.78 (m, 3H), 2 .06-2.08 (m, 1H), 2.18-2.22(m, 1H) 2.32-2.34 (m, 1H), 2.40-2.43 (m, 1H), 2.46-2.5 (m, 1H), 2.88-2.92 (m, 1H), 3.40 (s, 3H), 3.66-3.71 (m, 2H), 3. 73-3.77 (m, 1H), 3.87-3.91 (m, 4H), 3.92-3.94 (m, 2H) 3.96-3.98 (m, 1H), 4 .06-4.12 (m, 1H), 4.13-4.15 (m, 1H) 8.19 (s, 1H). MS m/z: 520 (M+1) 233

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(4-(methoxymethyl)-1H-1,2 ,3-triazol-1-yl)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.12-1.14 (d, 3H), 1.67-1.68 (m, 1H), 1.76-1.78 (d, 3H), 1.95-1.98 (m, 1H), 2.99 (s, 3H), 3.06 (s, 3H), 3.09-3.12 (m, 2H), 3.24-3, 26 (m, 1H), 3.40 (s, 3H), 3.41 (m, 1H), 3.67-3.72 (m, 3H), 3.97-3.99 (m, 2H) , 4.13-4.15 (m, 1H), 8.19 (s, 1H). MS m/z: 477 (M-1) 234

(4R,5S,6S)-6-((R)-1-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-methyl-7-oxo-3 -((3S,5S)-5-((sulfamoylamino)methyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.13-1.14 (d, 3H), 1.69-1.72 (m, 1H), 1.76-1.78 (d, 3H), 2.69-2.73 (m, 2H), 3.22-3.24 (m, 1H), 3.36 (s, 3H), 3.39-3.44 (m, 2H) 3.54 -3.55(m, 2H), 3.62-3.67(m, 2H), 3.92-3.99(m, 3H) 4.13-4.15(m, 1H), 8, 19 (s, 1H). MS m/z: 514 (M-1) 235

(4R,5S,6R)-3-((3S,5S)-5-(2-Amino-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-5-carbonyl)pyrrolidine-3- ylthio)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.14-1.18 (d, 3H), 1.35-1.36 (d, 3H), 1.95 (m, 1H), 2.66 ( d, 1H), 2.99-3.01 (m, 1H), 3.23-3.33 (d, 1H), 3.44-3.47 (m, 2H), 3.54-3, 59 (d, 2H), 3.81-3.89 (m, 3H), 4.03-4.08 (m, 2H), 4.40 (m, 2H), 4.64 (m, 1H) , 6.15-6.29 (t, 1H). MS m/z: 571 (M+1). 236

(4R,5S,6R)-3-((3S,5S)-5-(((R)-3-Aminopyrrolidine-1-sulfamido)methyl)pyrrolidin-3-ylthio)-6-((R)-1 -(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.02-1.2 (d, 3H), 1.21-1.27 (d, 3H), 1.7-1.72 (m, 1H), 2.13 (m, 1H), 2.46 (m, 1H), 2.68 (m, 1H), 3.34-3.45 (m, 6H), 3.60-3.65 (m, 5H), 3.83(m, 1H), 4.05(m, 1H), 4.43(m, 1H), 4.80(m, 1H), 6.02-6.09(t, 1H ). MS m/z: 566 (M+) 237

(4R,5S,6R)-3-((3S,5S)-5-(((S)-3-Aminopyrrolidine-1-sulfamido)methyl)pyrrolidin-3-ylthio)-6-((R)-1 -(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.20 (d, 3H), 1.28-1.30 (m, 3H), 1.9 (m, 1H), 2.16 ( m, 1H), 2.47-2.48 (m, 1H), 2.71-2.73 (m, 1H), 3.32-3.46 (m, 6H), 3.65 (m, 5H), 3.85(m, 1H), 4.12(m, 1H), 4.43(m, 1H), 4.47(m, 1H), 6.02-6.29(t, 1H ). MS m/z: 566 (M+) 238

(4R,5S,6R)-3-((3S,5S)-5-(3-((R)-3-Aminopyrrolidine-1-carbonyl)phenylcarbamoyl)pyrrolidin-3-ylthio)-6-((R) -1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.02-1.2 (d, 3H), 1.26-1.28 (d, 3H), 1.42 (m, 1H), 2.13- 2.49 (m, 3H), 3.59 (m, 2H), 3.63-3.66 (m, 2H), 3.34-3.89 (m, 2H), 3.94-3, 97 (m, 3H), 4.09-4.14 (m, 2H), 4.44 (m, 1H), 6.02-6.29 (m, 1H) 7.65-7.92 (m , 3H), 8.2 (s, 1H). MS m/z: 620 (M+) 239

(4R,5S,6S)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(sulfamoylamino)ethyl )-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.01-1.2 (d, 3H), 1.21-1.28 (d, 3H), 1.95 (m, 1H), 2.51- 2.53 (m, 1H), 2.91 (s, 3H), 3.01 (s, 3H), 3.35-3.43 (m, 2H), 3.65-3.67 (m, 2H), 3.80-3.84 (m, 2H), 4.08-4.09 (m, 2H). MS m/z: 462 (M+1) 240

(4R,5S,6S)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-(sulfamoylamino)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 0.97-1.09 (d, 3H), 1.23-1.29 (d, 3H), 2.13-2.25 (m, 4H), 2.63 (m, 2H), 2.79-2.82 (m, 2H), 3.35-3.50 (m, 2H), 3.61-3.64 (m, 1H), 3. 90 (m, 3H), 4.01 (m, 1H), 4.24 (m, 1H), 4.64 (m, 1H). MS m/z: 502 (M+) 241

(4R,5S,6R)-3-((3S,5S)-5-(Dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-guanidinoacetamido)ethyl)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.06-1.30 (d, 6H), 1.92 (m, 1H), 2.95 (s, 3H), 3.14 (s, 3H) , 3.32(m, 2H), 3.4(m, 2H), 3.73-3.76(m, 2H), 3.88-3.99(m, 2H), 4.02(m , 1H), 4.30-4.32 (m, 1H), 4.45 (m, 1H). MS m/z: 481 (M+) 242

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -guanidinoacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.19-1.22 (d, 3H), 1.26-1.30 (d, 3H), 1.72-1.83 (m, 1H), 2.15-2.18 (m, 1H), 2.33-2.35 (m, 1H), 2.43-2.46 (m, 1H), 2.74-2.78 (m, 1H ), 3.09-3.12 (m, 1H), 3.23-3.26 (m, 1H), 3.36-3.39 (m, 2H), 3.54-3.57 (m , 1H), 3.68-3.73 (m, 2H), 3.74-3.78 (m, 2H), 3.98-4.02 (m, 2H), 4.13-4.15 (m, 1H), 4.34-4.43 (m, 1H), 4.45-4.57 (m, 1H). 243

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-(((5-hydroxy-1-methyl-4 -oxo-1,4-dihydropyridin-2-yl)methyl)(methyl)carbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene -2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.07-1.17 (d, 3H), 1.37-1.38 (d, 3H), 3.04 (m, 2H), 1.86- 1.92(1H), 3.15(s, 3H), 3.31-3.37(m, 3H), 3.47(m, 1H), 3.74(s, 3H), 3.75 (m, 1H), 3.97 (m, 1H), 4.17 (m, 1H), 4.46 (m, 1H), 4.6-4.68 (m, 1H), 6.08- 6.29 (t, 1H), 6.38 (s, 1H), 7.65 (s, 1H). 244

(4R,5S,6R)-3-((3S,5S)-5-(Aminomethyl)pyrrolidin-3-ylthio)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4- methyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.21 (d, 3H), 1.35-1.37 (d, 3H), 1.89-1.93 (m, 1H), 2.06-2.08 (m, 1H), 2.44-2.68 (m, 1H), 3.08-3.12 (m, 1H), 3.34-3.35 (m, 1H ), 3.43-3.46 (m, 2H), 3.57-3.59 (m, 1H), 3.67-3.71 (m, 1H), 3.84-3.86 (m , 1H), 4.13-4.16 (m, 1H), 4.25-4.26 (m, 1H), 6.02-6.29 (t, 1H). MS m/z: 419 (M+1) 245

(4R,5S,6R)-6-((R)-1-(2-Aminoacetamido)ethyl)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine -3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.22 (d, 3H), 1.31-1.33 (d, 3H), 1.88-1.92 (m, 1H), 2.10-2.13(m, 1H), 2.22-2.24(m, 1H), 2.47-2.49(m, 1H), 2.89-2.93(m, 1H ), 3.23-3.27 (m, 1H), 3.38-3.40 (m, 1H), 3.48-3.49 (m, 1H), 3.57-3.58 (m , 2H), 3.63-3.67 (m, 1H), 3.70-3.72 (m, 1H), 3.78-3.80 (m, 2H), 3.84-3.86 (m, 2H), 3.91-4.05 (m, 1H), 4.13-4.16 (m, 1H), 4.34-4.36 (m, 1H), 4.44-4 .45 (m, 1H). 246

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((R)-3-((5-hydroxy -1-methyl-4-oxo-1,4-dihydropyridin-2-yl)methylamino)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2, 0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.20-1.22 (d, 3H), 1.35-1.37 (d, 3H), 1.84-1.88 (m, 1H), 1.98-2.00 (m, 1H), 2.22-2.27 (m, 1H), 2.88-2.92 (m, 1H), 3.36-3.43 (m, 2H ), 3.46-3.48 (m, 2H), 3.57-3.59 (m, 3H), 3.65-3.71 (m, 3H), 3.74-3.80 (m , 2H), 3.82-3.85 (m, 2H), 4.01-4.03 (m, 1H), 4.14-4.16 (m, 1H), 4.32-4.34 (m, 1H), 4.44-4.45 (m, 1H) 6.02-6.29 (t, 1H), 6.61 (s, 1H), 7.43 (s, 1H). MS m/z: 639 (M+1) 247

(4R,5S,6R)-6-((R)-1-(2,2-Difluoroacetamido)ethyl)-3-((3S,5S)-5-((3S,4S)-3-guanidino-4 -hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) δ ppm: 1.25-1.27 (d, 3H), 1.35-1.37 (d, 3H), 1.96-1.98 (m, 1H), 2.06-2.10 (m, 1H), 3.02-3.04 (m, 1H) 3.20-3.22 (m, 1H), 3.34-3.38 (m, 1H) , 3.41-3.48 (m, 1H), 3.60-3.64 (m, 1H), 3.69-3.78 (m, 2H), 3.90-3.93 (m, 1H), 4.00-4.02 (m, 1H), 4.25-4.26 (m, 1H), 4.27-4.27 (m, 1H), 4.28-4.30 ( m, 1H), 4.43-4.51 (m, 2H) 6.02-6.29 (t, 1H). MS m/z: 559 (M+) 248

(4R,5S,6R)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-3-((3S,5R)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4- methyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.28 (d, 3H), 1.36 (d, 3H), 2.38-2.50 (m, 1H), 2.96 (s, 3H), 2 .99 (m, 2H), 3.01 (m, 1H), 3.29 (m, 1H), 3.36 (s, 3H), 3.42-3.5 (m, 1H), 3. 61-3.68 (m, 1H), 4.01 (d, 1H), 4.18 (d, 1H), 4.44-.4.47 (m, 1H), 6.03-6.29 (t, 1H). mass-(460.50) 461.1 249

(4R,5S,6R)-6-((R)-1-((2R,4S)-4-aminopyrrolidine-2-carboxamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine -3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.28 (d, 3H), 1.34 (m, 1H), 1.57 (m, 1H), 1.82 (m , 1H), 2.08 (d, 1H), 2.30 (m, 1H), 2.30 (m, 1H), 2.99 (s, 3H), 3.12 (d, 3H), 3 .32-3.46(m, 3H), 3.60-3.81(m, 2H), 4.00(d, 2H), 4.42(m, 1H), 4.59(m, 1H ), 4.72 (m, 1H), 5.25 (m, 1H). mass (494.61) 495.1. 250

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(( 2R,4S)-4-aminopyrrolidine-2-carboxamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.10 (d, 3H), 1.21 (d, 3H), 1.98 (m, 1H), 2.15 (m, 1H), 2.55 (m , 2H), 2.89 (m, 1H), 3.27-3.45 (m, 2H), 3.41 (d, 1H), 3.59 (m, 5H), 3.84 (d, 2H), 3.96(m, 1H), 4.56(m, 1H), 4.74(m, 1H), 5.28(m, 1H). mass (535.66) 536.2. 251

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-amino-2-(fluoromethyl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6- ((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.37 (d, 3H), 1.47 (m, 1H), 1.92-2.03 (m, 2H), 2 .40 (m, 1H), 3.07 (d, 2H), 3.37-3.44 (m, 2H), 3.54-3.75 (m, 6H), 4.18 (d, 1H ), 4.47 (d, 1H), 4.67-4.86 (m, 1H), 5.42-5.62 (dd, 1H), 6.08-6.29 (t, 1H). mass (533.56) 533.1. 252

(4R,5S,6R)-4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-3-((3S,5S)-5-((piperazine -1-sulfamido)methyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.32 (d, 3H), 1.62-1.68 (m, 1H), 1.76-1.83 (m, 1H), 2.45-2.51(m, 2H), 2.60-2.66(m, 2H), 2.73(s, 3H), 2.78(m, 1H), 3.32 -3.37(m, 3H), 3.44-3.48(m, 3H), 3.55-3.61(m, 2H), 3.72-3.78(m, 2H), 3 .81-3.90 (m, 3H), 4.12-4.16 (dd, 1H), 4.44-4.48 (m, 1H). mass (559.70) 560.1. 253

(4R,5S,6R)-3-((3S,5S)-5-(((S)-3-aminopyrrolidine-1-sulfamido)methyl)pyrrolidin-3-ylthio)-4-methyl-6-(( R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.29 (d, 3H), 1.79-1.83 (m, 1H), 2.08-2.12 (m, 1H), 2.44-2.50 (m, 2H), 2.73 (m, 2H), 2.75 (d, 2H), 3.30-3.33 (m, 2H), 3.46 (m, 2H), 3.48 (m, 2H), 3.52 (m, 1H), 3.59 (m, 1H), 3.59-3.62 (m, 1H), 3.72- 3.79 (m, 1H), 3.84 (m, 1H), 3.86 (m, 1H), 4.04-4.05 (m, 1H), 4.14-1.16 (m, 1H), 4.36-4.39 (m, 1H), 4.44-4.48 (m, 1H). mass (559.70) 560.2. 254

(4R,5S,6R)-3-((3S,5S)-5-((5-hydroxy-1-methyl-4-oxo-1,4-dihydropyridine-2-carboxamido)methyl)pyrrolidin-3-ylthio )-4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.29 (d, 3H), 1.69 (m, 1H), 2.74 (m, 1H), 2.75 (d , 6H), 3.28-3.38 (m, 2H), 3.55 (m, 2H), 3.73 (m, 1H), 3.76-3.84 (m, 1H), 3, 90 (s, 3H), 4.47 (s, 3H), 6.74 (s, 1H), 7.06 (s, 1H). mass (562.64) 561.1 255

(4R,5S,6R)-3-((3S,5S)-5-(((1S,3R)-3-aminocyclopentanecarboxamido)methyl)pyrrolidin-3-ylthio)-4-methyl-6-((R) -1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.29 (d, 3H), 1.84-1.89 (m, 2H), 1.91 (m, 3H), 1 .96-1.98 (m, 1H), 2.32-2.39 (m, 1H), 2.63-2.70 (m, 1H), 3.75 (s, 3H), 2.97 -3.01 (m, 1H), 3.28-3.38 (m, 2H), 3.54 (d, 1H), 3.58-3.59 (dd, 3H), 3.78-3 .85 (m, 2H), 3.86 (d, 2H), 3.97 (br, 1H), 4.14 (d, 1H), 4.44-4.47 (m, 1H). masses (522.66) 522. 256

(4R,5S,6R)-3-(1-(4,5-dihydrothiazol-2-yl)azetidin-3-ylthio)-4-methyl-6-((R)-1-(2-(methylamino) acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16-1.18 (d, 3H), 1.25-1.27 (d, 3H), 1.92 (s, 1H), 2.77 (s, 3H), 3.17-3.21(m, 3.56-3.58(m, 1H), 3.60-3.64(m, 2H), 3.87(d, 2H), 3, 97-4.01 (m, 2H), 4.10-4.13 (dd, 1H), 4.15 (br s, 1H), 4.18-4.25 (m, 2H), 4.34 -4.35 (m, 1H), 4.44-4.47 (m, 1H), 4.69-4.71 (m, 2H), wt (453.58) 454.1 257

(4R,5S,6R)-3-(2-(2-(aminomethyl)-5-hydroxy-4-oxopyridin-1(4H)-yl)ethylthio)-4-methyl-6-((R)-1 -(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.05 (d, 3H), 1.24 (d, 3H), 1.39-1.42 (m, 1H), 1.92 (s, 1H), 2 .77 (d, 2H), 2.80 (m, 2H), 2.98 (m, 1H), 3.05-3.21 (m, 1H), 3.44-3.49 (m, 2H ), 3.51-3.55 (m, 1H), 3.72-3.74 (m, 1H), 3.92-4.03 (m, 3H), 4.1-4.25 (m , 2H), 4.40 (d, 3H), 6.62 (d, 1H), 7.70 (s, 1H). mass (479.55) 480.1 258

(4R,5S,6R)-3-((3S,5S)-5-(((1S,3R)-3-aminocyclopentanecarboxamido)methyl)pyrrolidin-3-ylthio)-6-((R)-1-( 2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.31 (d, 3H), 1.84-1.86 (m, 1H), 2.07-2.08 (m, 2H), 2.32-2.33(m, 2H), 2.46-4.48(m, 3H), 2.97-2.98(m, 2H), 3.32-3.33( m, 2H), 3.50-3.52 (m, 2H), 3.72-3.74 (m, 2H), 3.98-4.01 (m, 1H), 3.4.014-4, 17 (m, 1H), 4.27-4.29 (m, 1H) 4.45-54.48 (m, 1H) 6.16 (t, 1H). mass -(529.60) 530. 259

(4R,5S,6R)-3-((3S,5S)-5-(((2S,4S)-4-aminopyrrolidine-2-carboxamido)methyl)pyrrolidin-3-ylthio)-6-((R) -1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 1H NMR (D2O) -1.21 (d, 3H), 1.35 (d, 3H), 2.46-2.48 (m, 1H), 2.61-2.68 (m, 2H), 3.05 (d, 1H), 3.34 (m, 2H), 3.58-3.65 (m, 4H), 3.89-4.16 (m, 3H), 4.10 (d, 1H), 4.44 (d, 1H), 6.15 (t, 1H). mass (530.59) 531.2. 260

(4R,5S,6R)-3-((3S,5S)-5-(((1R,3S)-3-aminocyclopentanecarboxamido)methyl)pyrrolidin-3-ylthio)-6-((R)-1-( 2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.33 (d, 3H), 1.84-1.87 (m, 1H), 2.08-2.11 (m, 2H), 2.31-2.33(m, 2H), 2.64-2.68(m, 2H), 2.86-2.99(m, 2H), 3.33-3.35( m, 2H), 3.49 (m, 1H), 3.52-3.56 (m, 2H), 3.60-3.64 (m, 1H), 3.68-3.69 ( m, 1H), 3.71 (m, 1H), 3.77-3.79 (m, 1H), 4.14-4.16 (m, 1H), 4.30-.4.47 (m , 1H), 6.16 (t, 1H). mass (529.60) 530.2. 261

(4R,5S,6R)-3-((3S,5S)-5-(((2S,4R)-4-aminopyrrolidine-2-carboxamido)methyl)pyrrolidin-3-ylthio)-6-((R) -1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.36 (d, 3H), 2.32-2.33 (m, 1H), 2.45-2.48 (m, 2H), 3.07-3.10 (m, 1H), 3.30-3.33 (m, 4H), 3.52-3.57 (m, 4H), 3.74-3.79 ( m, 3H), 3.91-3.94 (m, 3H), 4.07-4.11 (m, 2H), 6.15 (t, 1H). mass (530.59) 531.2. 262

(4R,5S,6R)-3-((3S,5S)-5-(((1R,3S)-3-aminocyclopentanecarboxamido)methyl)pyrrolidin-3-ylthio)-4-methyl-6-((R) -1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.28 (d, 3H), 1.84-1.89 (m, 2H), 1.96-1.98 (m, 1H), 2.32-2.39 (m, 2H), 2.63-2.70 (m, 2H), 3.75 (s, 3H), 2.97-3.01 (m, 2H) , 3.28-3.38 (m, 2H), 3.54 (d, 1H), 3.58-3.59 (dd, 3H), 3.78-3.85 (m, 2H), 3 .86 (d, 2H), 3.97 (br, 1H), 4.14 (d, 1H), 4.44-4.47 (m, 1H). masses (522.66) 523. 263

(4R,5S,6R)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-3-(1-(4,5-dihydrothiazol-2-yl)azetidin-3-ylthio)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.36 (d, 3H), 3.18-3.19 (m, 1H), 3.56-3.62 (m, 2H), 3.63-3.65(m, 2H), 3.98-4.01(m, 2H), 4.12-4.14(m, 1H), 4.23-4.26( m, 1H), 4.42-4.46 (m, 2H), 4.56 (m, 2H), 6.16 (t, 1H). mass (460.52) 461.0. 264

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-amino-2-methylpiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6 -((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.32 (d, 3H), 1.78-1.81 (m, 1H), 2.2 (m, 1H), 2 .76 (s, 3H), 2.86 (m, 2H), 3.20-3.22 (m, 2H), 3.32-3.36 (m, 3H), 3.57-3.58 (m, 2H), 3.76-3.78 (m, 3H), 3.84-3.85 (m, 3H), 3.89 (m, 2H), 4.12-4.15 (m , 1H), 4.29-4.37 (m, 2H), 4.4-4.48 (m, 1H). mass (522.66) 523.2. 265

(4R,5S,6R)-3-(((2S,4S)-1-acetyl-4-aminopyrrolidin-2-yl)methylthio)-6-((R)-1-(2,2-difluoroacetamido)ethyl )-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.36 (d, 3H), 1.99-2.01 (m, 1H), 2.16 (s, 3H), 2 .7-2.75 (m, 1H), 2.87-2.92 (m, 1H), 3.41-3.44 (m, 1H), 3.48 (m, 1H), 3.57 -3.59 (m, 2H), 3.86-3.90 (m, 1H), 4.10-4.13 (m, 2H), 4.22-4.24 (m, 1H), 4 .42-4.47 (m, 1H), 6.16 (t, 1H). mass (460.50) 461.1. 266

(4R,5S,6R)-6-((R)-1-((1S,3R)-3-aminocyclopentanecarboxamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio )-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.27 (d, 3H), 1.37 (d, 3H), 1.8-1.86 (m, 2H), 1.91-1.96 (m, 2H), 2.14-2.20 (m, 2H), 2.31-2.33 (m, 1H), 2.59-2.60 (m, 1H), 2.95-296 (m, 1H), 2.99 (s, 3H), 3.07 (s, 3H), 3.21,3.22 (m, 1H), 3.40-3.45 (m, 2H), 3.73 -3.77(m, 2H), 3.91(m, 1H), 4.13-4.15(m, 1H), 4.43-4.47(m, 2H). masses (493.62) 494. 267

(4R,5S,6R)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-3-(((2S,4S)-4-(sulfamoylamino) pyrrolidin-2-yl)methylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.36 (d, 3H), 1.71-1.73 (m, 1H), 2.60-2.68 (m, 1H), 3.05-3.07(m, 1H), 3.16-3.18(m, 2H), 3.33-3.35(m, 2H), 3.57-3.58( m, 2H), 3.603.63 (m, 1H), 4.06-4.08 (m, 2H), 4.43-4.47 (m, 1H), 6.16 (t, 1H). mass (497.54) 498.0. 268

(4R,5S,6R)-6-((R)-1-(3-amino-3-oxopropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.42 (d, 3H), 1.92 (s, 3H), 3.04 (s, 5H), 3.28-3 .31 (m, 2H), 3.34-3.38 (m, 2H), 3.41-3.48 (t, 1H), 3.53-3.65 (m, 2H), 3.91 -3.99 (m, 3H), 4.16 (d, 1H), 4.35-4.39 (q, 1H), 4.55-4.58 (dd, 1H), 4.61-4 .65 (m, 2H). masses (467.54) -468.1. 269

(4R,5S,6R)-4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-3-(((2S,4S)-4-(sulfamoylamino )pyrrolidin-2-yl)methylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.24 (d, 3H), 1.30 (d, 3H), 1.47-1.48 (m, 4H), 2.43-2.50 (m, 1H), 2.63-2.72(m, 4H), 2.75(s, 3H), 3.18-3.23(q, 2H), 3.32-3.35(m, 1H) , 3.59-3.65(m, 1H), 3.72-3.79(m, 1H), 3.84(m, 2H), 4.13-4.23(m, 1H), 4 .36-4.47 (m, 1H). mass (490.60) 491.2. 270

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-((R) -thiazolidine-4-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.31 (d, 3H), 1.52 (s, 1H), 1.91 (m, 2H), 2.68 (s , 1H), 2.99 (s, 4H), 3.07 (s, 3H), 3.14-3.35 (m, 1H), 3.35 (m, 3H), 3.59 (m, 2H), 4.00 (m, 2H), 4.12-4.17 (m, 2H), 4.27-4.39 (m, 2H), 4.57-4.73 (m, 2H) . mass (497.63) 498.1. 271

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-((R)-thiazolidine-4-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.32 (d, 3H), 1.52 (m, 1H), 1.84 (m, 1H), 1.91 (m , 1H), 2.12 (m, 1H), 2.24 (m, 1H), 2.48 (m, 2H), 2.68 (m, 2H), 2.84 (m, 2H), 3 .12-3.15 (m, 4H), 3.37 (m, 2H), 3.58-3.61 (m, 2H), 3.70-3.76 (m, 2H), 3.87 (s, 2H), 3.99-4.25 (m, 4H), 4.39-4.71 (m, 1H). masses (538.68) 537. 272

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(3-(methylamino)-3 -oxopropanamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.33 (d, 3H), 1.46 (d, 3H), 1.92-1.97 (m, 2H), 2.56 (m, 1H), 2 .73 (s, 3H), 2.76 (s, 3H), 2.95-299 (m, 2H), 3.07 (m, 2H), 3.09 (m, 2H), 3.11 ( m, 1H), 3.25-3.29 (m, 2H), 3.36-3.4 (m, 2H), 3.71-3.77 (m, 1H), 3.92-3, 98 (m, 2H), 4.12-4.75 (m, 2H). mass (481.57) 482.2 273

(4R,5S,6R)-3-((R)-2-amino-3-((R)-3-aminopyrrolidin-1-yl)-3-oxopropylthio)-4-methyl-6-((R) -1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.24 (d, 3H), 1.33 (d, 3H), 1.82-1.83 (m, 2H), 2.53-2.56 (m, 2H), 2.76 (s, 3H), 3.05 (m, 2H), 3.17-3.20 (m, 2H), 3.32-3.37 (m, 2H), 3.72 -3.73 (m, 2H), 3.78 (d, 2H), 4.02-4.07 (m, 2H). mass (468.57) 469.5 274

(4R,5S,6R)-6-((R)-1-(butylamino)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -0.96 (s, 3H), 1.22 (d, 3H), 1.25 (d, 3H), 1.31 (d, 3H), 1.49-1 .56 (m, 2H), 2.99 (m, 1H), 3.04 (s, 3H), 3.07 (s, 3H), 3.09 (m, 1H), 3.35-3, 45 (m, 2H), 3.58-3.59 (m, 1H), 3.72-3.73 (m, 1H), 3.82 (m, 1H), 3.86 (m, 1H) , 4.00 (m, 1H), 4.26 (d, 1H), 4.62 (m, 1H). mass (438.58) 439.2 275

(4R,5S,6R)-3-((3S,5S)-5-(4-amino-4-benzylpiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.24 (d, 3H), 1.33 (d, 3H), 1.82-1.83 (m, 2H), 2.53-2.56 (m, 2H), 2.76 (s, 3H), 3.05 (m, 3H), 3.17-3.20 (m, 4H), 3.32-3.37 (m, 4H), 3.72 -3.73(m, 2H), 3.72-3.73(m, 2H), 3.78(d, 2H), 4.02-4.07(m, 2H), 7.31(d , 2H), 7.45 (d, 2H). mass (598.76) 599.5 276

(4R,5S,6R)-3-((3S,5S)-5-((1R,5S,8S)-8-amino-3-azabicyclo[3.2.1]octane-3-carbonyl)pyrrolidine- 3-ylthio)-4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.29 (d, 3H), 1.55-1.64 (m, 3H), 1.78 (m, 1H), 2 .43-2.47(m, 3H), 2.76(s, 3H), 2.97(m, 1H), 3.12(m, 1H), 3.33(m, 1H), 3, 44-3.47(m, 2H), 3.58-3.78(m, 3H), 3.86(d, 2H), 3.99(m, 1H), 4.08-4.13( m, 2H), 4.40 (m, 1H), 4.49 (m, 1H), 4.55-4.59 (m, 1H). mass (522.66) 523.2 277

(4R,5S,6R)-3-((3S,5S)-5-(4-amino-4-carbamoylpiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.35 (d, 3H), 1.74-1.81 (m, 2H), 2.00-2.12 (m, 4H), 2.47-2.58 (m, 1H), 2.76 (s, 3H), 3.00-3.05 (m, 1H), 3.34-3.46 (m, 2H) , 3.59-3.68 (m, 2H), 3.72-3.78 (m, 2H), 3.81 (m, 1H), 3.85 (m, 1H), 3.89 (d , 2H), 4.05 (d, 1H), 4.37 (m, 1H), 4.45-4.48 (m, 1H), 4.71-4.76 (m, 1H). mass (551.66) 552.2 278

(4R,5S,6R)-3-((3S,5S)-5-(4-amino-4-carbamoylpiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.33 (d, 3H), 1.50 (s, 3H), 1.81-1.84 (m, 3H), 2 .43-2.50 (m, 2H), 2.76 (s, 3H) 2.90-.299 (m, 1H), 3.20-3.33 (m, 2H), 3.38-3 .50 (m, 2H), 3.59-3.60 (m, 1H), 3.72-3.78 (m, 2H), 3.88 (d, 2H), 3.96 (m, 1H ), 4.05-4.08 (m, 2H), 4.46-4.49 (m, 1H), 4.54-4.56 (m, 1H). mass (522.66) 523.4 279

(4R,5S,6R)-4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-3-((3S,5S)-5-(tetrahydro- 2H-pyran-4-ylcarbamoyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.36 (d, 3H), 1.57-1.60 (m, 2H), 1.87 (m, 2H), 2 .06 (m, 2H), 2.56-2.60 (m, 2H), 2.76 (s, 3H), 3.07 (m, 1H), 3.20-3.22 (m, 1H ), 3.35-3.42 (m, 2H), 3.54-3.59 (m, 2H), 3.72 (m, 2H), 3.97 (m, 1H), 4.00- 4.09 (m, 2H), 4.12-4.14 (m, 1H), 4.46 (m, 1H). mass (509.62) 509.61. 280

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-((R)-1,1-dioxothiazolidine-4-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.33 (d, 3H), 1.92-1.95 (m, 1H), 2.26 (m, 2H), 2 .47-2.52 (m, 2H), 2.75-2.78 (m, 2H), 2.95-3.00 (m, 2H), 3.30-3.39 (m, 2H) , 3.61-3.67 (m, 3H), 3.70-3.79 (m, 2H), 3.91 (m, 2H), 4.07-4.26 (m, 1H), 4 .26-4.28 (m, 2H), 4.41-4.47 (m, 1H). mass (570.68) 570.1 281

(4R,5S,6R)-4-methyl-7-oxo-3-((3S,5S)-5-((sulfamoylamino)methyl)pyrrolidin-3-ylthio)-6-((R)-1-( (R)-1,1-dioxothiazolidine-4-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.24 (d, 3H), 1.33 (d, 3H), 1.74-1.78 (m, 2H), 2.79-2.81 (m, 2H), 3.32-3.49 (m, 4H), 3.52-3.55 (m, 2H), 3.63-3.68 (m, 1H), 3.93-3.96 ( m, 1H), 4.03-4.06 (m, 1H), 4.10-4.13 (m, 2H), 4.40-4.49 (m, 2H). mass (566.67) 566.5 282

(4R,5S,6R)-3-((3S,5S)-5-(((2S,4S)-4-fluoropyrrolidine-2-carboxamido)methyl)pyrrolidin-3-ylthio)-4-methyl-6- ((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.28 (d, 3H), 1.86 (m, 2H), 2.08 (m, 2H), 2.23 (m , 1H), 2.47-2.48 (m, 1H), 2.60-2.68 (m, 1H), 2.70 (m, 1H), 2.75 (s, 3H), 3, 33-3.42 (m, 3H), 3.56-3.63 (m, 2H), 3.72-3.76 (m, 2H), 3.86 (d, 2H), 4.05 ( m, 1H), 4.13-4.16 (m, 1H), 4.40-4.43 (m, 1H), 5.30-5.49 (d, 1H). mass (526.62) 527.1. 283

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine- 3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.28 (d, 3H), 1.34 (d, 3H), 1.97-1.99 (m, 1H), 2.99 (s, 3H), 3 .00 (s, 3H), 3.04 (m, 1H), 3.31-3.36 (m, 1H), 3.44-3.48 (m, 1H), 3.57-3.60 (m, 1H), 3.73-3.77 (m, 1H), 4.05 (m, 1H), 4.13-3.16 (m, 1H), 4.40-4.43 (m , 1H), 5.42 (d, 2H), 9.27 (s, 1H). mass (492.55) 493.8 284

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-((R) -1,1-dioxothiazolidine-4-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.29 (d, 3H), 1.36 (d, 3H), 1.84 (m, 1H), 2.60-2.79 (m, 2H), 3 .00 (s, 3H), 3.05 (m, 1H), 3.07 (s, 3H), 3.38 (m, 2H), 3.48 (d, 2H), 3.63 (m, 2H), 3.76(m, 1H), 4.06-4.17(m, 2H), 4.42(m, 2H). mass (529.63) 529.1. 285

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-((R) -piperazine-2-carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.31 (d, 3H), 1.92 (m, 1H), 2.94 (d, 3H), 3.00 (d , 3H), 3.04 (m, 2H), 3.07 (m, 2H), 3.20-3.25 (m, 2H), 3.48 (m, 2H), 3.59-3, 60 (m, 4H), 3.96 (m, 2H), 3.99-4.00 (m, 1H), 4.52-4.55 (m, 1H). mass (494.61) 495.1 286

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((1R)-1-((2R)-2-(3-(( R)-1-hydroxyethyl)-4-oxoazetidin-2-yl)propanamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.27 (m, 6H), 1.33 (d, 3H), 1.39 (d, 3H), 2.98 (d, 1H), 2.99 (s , 3H), 3.07 (s, 3H), 3.08 (m, 1H), 3.18-3.20 (m, 1H), 3.40-3.44(m, 2H), 3, 55-3.58 (m, 1H), 3.71-3.76 (m, 1H), 3.86-3.88 (m, 1H), 3.95-3.96 (m, 2H), 3.99-4.02(m, 2H), 4.10(m, 1H), 4.52-4.55(m, 1H). masses (551.66) 552. 287

(4R,5S,6R)-3-((3S,5S)-5-((2R,4S)-4-amino-2-methylpyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6 -((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.24 (d, 3H), 1.31 (d, 3H), 1.35 (d, 3H), 1.72-1.75 (m, 1H), 2 .08 (m, 1H), 2.45 (m, 2H), 2.70 (m, 2H), 2.76 (s, 3H), 2.89 (m, 1H), 3.29-3, 40 (m, 2H), 3.58 (m, 2H), 3.74-3.76 (m, 1H), 3.96 (d, 2H), 4.15 (d, 2H), 4.21 -4.23(m, 1H), 4.45-4.46(m, 1H). mass (508.63) 509. 288

(4R,5S,6R)-3-((3S,5S)-5-((2S,4S)-4-amino-2-phenylpyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6 -((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.23 (d, 3H), 1.32 (d, 3H), 1.92 (m, 1H), 2.46 (m, 1H), 2.76 (s , 3H), 2.98 (m, 1H), 3.34 (m, 1H), 3.52-3.89 (m, 4H), 3.94-3.95 (m, 2H), 4, 02-4.08 (m, 2H), 4.11-4.14 (m, 2H), 4.47 (m, 1H), 7.37-7.50 (m, 5H). mass (570.70) 571.3. 289

(4R,5S,6R)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-7-oxo-3-((S)-piperazin-2-ylmethylthio)-1 -azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.26 (d, 3H), 1.36 (d, 3H), 2.75-2.81 (m, 2H), 2.94-3.00 (m, 1H), 3.21-3.28 (m, 3H), 3.34-3.42 (m, 2H), 3.55-3.58 (m, 2H), 4.15 (d, 2H) , 4.46 (m, 1H), 6.16 (t, 1H). mass (418.46) 419.2. 290

(4R,5S,6R)-3-((3S,5S)-5-((1R,4R)-2,5-diazabicyclo[2,2,1]heptane-2-carbonyl)pyrrolidin-3-ylthio) -4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.26 (d, 3H), 1.36 (d, 3H), 1.39-1.46 (m, 1H), 1.89 (m, 1H), 2 .28 (m, 1H), 2.76 (m, 3H), 2.98 (m, 1H), 3.36-3.42 (m, 1H), 3.49 (m, 3H), 3. 58 (m, 1H), 3.65 (m, 1H), 3.74-3.76 (m, 2H), 3.87 (d, 2H), 3.98 (m, 1H), 4.13 (d, 1H), 4.26 (m, 1H), 4.47 (m, 1H), 4.60 (m, 2H). mass (506.62) 507.3 291

(4R,5S,6R)-4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-3-((3S,5S)-5-((( R)-thiazolidine-4-carboxamido)methyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.11 (d, 3H), 1.26 (d, 3H), 1.55 (m, 1H), 1.69 (m, 1H), 1.92 (s , 2H), 2.67 (m, 1H), 2.70-2.76 (m, 3H), 3.18-3.22 (m, 1H), 3.56-3.60 (m, 2H ), 3.91-3.92 (m, 1H), 3.98 (d, 3H), 4.12-4.15 (m, 3H), 4.44 (m, 1H), 4.46- 4.47 (m, 1H), 4.69 (m, 1H), 4.82 (m, 1H). mass (526.67) 527.1. 292

(4R,5S,6R)-3-((3S,5S)-5-(3-amino-3-methylazetidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 6H), 1.67 (d, 3H), 1.92 (d, 3H), 2.46-2.47 (m, 1H), 2 .60-2.61 (m, 2H), 2.76-2.78 (m, 2H), 3.32 (m, 1H), 3.85 (m, 2H), 3.88-3.89 (m, 2H), 4.17 (m, 2H), 4.42-4.46 (m, 2H), 4.81-4.84 (m, 2H). mass (494.61) 495.2 293

(4R,5S,6R)-6-((R)-1-(cyclopropylmethylamino)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -0.71 (d, 3H), 1.23 (d, 3H), 1.28-1.29 (m, 2H), 1.46-1.49 (m, 2H), 1.57-1.58 (m, 1H), 2.32 (m, 1H), 2.94-2.99 (m, 1H), 3.02-3.06 (m, 1H) , 3.10-3.11 (m, 2H), 3.12-3.13 (m, 2H), 3.16-3.19 (m, 1H), 3.42-3.46 (m, 2H), 3.73 (m, 2H), 3.75-3.88 (m, 2H), 3.89-3.91 (m, 1H), 4.25-4.27 (m, 1H) , 4.73-4.74 (m, 1H), 4.80 (m, 1H). mass (436.57) 437.4. 294

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(1-(4,5-dihydrothiazol-2-yl) azetidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.33 (d, 3H), 3.55-3.62 (m, 2H), 3.98-4.01 (m, 2H), 4.11 (d, 2H), 4.19-4.24 (m, 2H), 4.35-4.42 (m, 1H), 4.73 (d, 2H), 4.85 (d, 2H), 5.41 (d, 2H), 9.27 (s, 1H). mass (492.58) 493.4 295

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(5-(( methylamino)methyl)-1,3,4-oxadiazol-2-yl)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.31 (d, 3H), 1.92-1.96 (m, 3H), 2.72-2.76 (s, 3H), 2.99-3.00 (s, 3H), 3.15 (m, 3H), 3.38-3.39 (m, 3H), 4.07 (d, 4H), 4.39 -4.45 (m, 4H). mass (535.62) 536 296

(4R,5S,6R)-6-((R)-1-(2-(1H-1,2,3-triazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5 -(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.24 (d, 3H), 1.34 (d, 3H), 3.00-3.11 (s, 3H), 3.31-3.35 (s, 3H), 3.40 (d, 2H), 3.43 (d, 2H), 3.56 (d, 2H), 3.67-3.71 (m, 2H), 4.13 (d, 1H ), 4.37-4.43(m, 1H), 4.71-4.74(m, 1H), 5.28-5.30(m, 2H), 7.85(s, 1H). mass (491.56) 492.6 297

(4R,5S,6R)-3-((3S,5S)-5-((3R,4R)-3-amino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6 -((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.29 (d, 3H), 1.92 (m, 1H), 2.75-2.78 (m, 2H), 2 .90-2.91 (d, 1H), 3.25-3.27 (m, 1H), 3.55-3.58 (m, 1H), 3.69 (m, 1H), 3.72 (m, 1H), 3.74 (d, 1H), 3.80 (m, 1H), 3.83 (s, 3H), 3.85 (m, 1H), 3.88 (d, 1H) , 3.92 (m, 1H), 4.14 (d, 1H), 4.36 (d, 1H), 4.47 (d, 1H), 4.51 (d, 1H), 4.61 ( e, 1H). mass (510.61) 511.2

Preparation of Example 298: (4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-( (R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid

Step 1: (R)-4-Nitrobenzyl 4-((2R,3R)-3-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-oxoazetidine-2 -yl)-2-diazo-3-oxopentanoate

1H-Tetrazole-1-acetic acid (6.33 g, 49 mmol) was placed in a round bottom flask. To this was added ethyl acetate (1.5 L), TBTU (18.7 g, 58 mmol), diisopropylethylamine (14 ml, 80.38 mmol) under N ₂ atmosphere, and the reaction mixture was stirred for 1 hour. Trifluoroacetate salt of (R)-4-nitrobenzyl 4-((2R,3R)-3-((R)-1-aminoethyl)-4-oxoazetidin-2-yl)-2-diazo-3-oxopentanoate (17.5 g, 44 mmol) was diluted with ethyl acetate (75 ml) and neutralized using diisopropylethylamine (5 ml) at 0°C. Then, this solution was added to the reaction mixture above at 0 ^° C. under N ₂ atmosphere. After completion of the addition, the reaction mixture was warmed to room temperature and stirred for 14 hours under N ₂ . After completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried using sodium sulfate and evaporated in vacuo. Then, the crude residue was purified by column chromatography to give the product (14 g, 63%). ¹ H NMR (DMSO-d ₆ , 400 MHz): 9.35 (1H, s), 8.44-8.42 (1H, d), 8.31 (1H, s), 8.27-8, 25(2H, d), 7.72-7.70(2H, d), 5.45-5.44(2H, d), 5.23-5.09(2H, m), 4.08- 4.02(1H, m), 3.64-3.63(1H, t), 3.45-3.43(1H, q), 2.94-2.78(1H, q), 1, 2-1.19(3H, d), 1.17-1.16(3H, d).

Step 2: (4R,5R,6R)-4-Nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(diphenoxyphosphoryloxy)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

(R)-4-Nitrobenzyl 4-((2R,3R)-3-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-oxoazetidin-2-yl) -2-diazo-3-oxopentanoate (4 g, 8 mmol) was dissolved in 100 ml of acetone under N ₂ atmosphere. Rhodium octanoate (100 mg, 0.128 mmol) was added to this solution and heated at 60° C. for 2.5 hours. Then, after completion of the reaction, the reaction mixture was cooled to -30°C and diphenyl chlorophosphate (2.72 ml, 12.8 mmol), diisopropylethylamine (2.6 ml, 13.6 mmol) and a catalytic amount of dimethylaminopyridine (292 mg, 2.4 mmol). Then, the reaction mixture was stirred for 1 hour at -10°C. Diisopropylethylamine (1.7 ml) and pH=7 buffer solution were added and the reaction mixture was quenched with water. The aqueous layer was extracted with dichloromethane and the organic layer was evaporated in vacuo at room temperature. The oil thus obtained was purified by column chromatography to give the product as a solid residue (2.7 g, 47%). ¹ H NMR: 9.35 (1H, s), 8.62-8.60 (1H, d), 8.14-8.12 (2H, m), 7.62-7.60 (2H, d ), 7.46-7.37(4H, m), 7.32-7.20(6H, m), 5.33-5.31(2H, d), 5.28-5.24(2H , q), 4.23-4.21 (1H, d), 4.17-4.14 (1H, m), 3.59-3.56 (1H, q), 3.5-3.4 (1H, d), 1.23-1.21 (3H, d), 1.18-1.17 (3H, d).

Step 3: (4R,5S,6R)-4-nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S, 5S)-1-((4-nitrobenzyloxy)carbonyl)-5-((R)-3-((4-nitrobenzyloxy)carbonylamino)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-7-oxo-1- azabicyclo[3,2,0]hept-2-ene-2-carboxylate

(4R,5R,6R)-4-nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(diphenoxyphosphoryloxy)-4-methyl-7-oxo -1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (1.5 g, 21 mmol) was taken up in acetonitrile (150 ml) at 0°C. Then, the solution was degassed for 10 minutes using N ₂ atmosphere. To this solution was added thiol (1.22 g, 21 mmol) at 0° C. under N ₂ , followed by the addition of diisopropylethylamine (0.58 ml, 1.5 eq.). The resulting solution was degassed again for 15 minutes. The reaction mixture was stirred under N ₂ at 0° C. for 2 hours. After completion of the reaction, the reaction mixture was quenched using water and extracted with ethyl acetate. Then, the organic layer was washed with water, brine, dried over sodium sulfate and evaporated in vacuo to give a crude residue. The crude reaction mixture was purified by column chromatography to give the product (1.45 g, 66%) as a solid residue. M/S: 1027 (M+1); HPLC: 85.35%; ¹ H NMR (DMSO-d6, 400 MHz): 9.345 (1H, d), 8.64-8.61 (1H, t), 8.24-8.22 (5H, m), 7.77-7 .70 (2H, t), 7.65-7.60 (2H, t), 7.54-7.52 (1H, d), 7.49-7.47 (1H, d), 5.76 -5.45 (2H, d), 5.33-5.29 (2H, d), 5.24-5.20 (1H, d), 5.17-5.12 (2H, d), 5 .07-5.04 (2H, d), 4.64-4.62 (1H, d), 4.21-4.12 (4H, m), 3.91-3.83 (2H, d) , 3.59-3.53(2H, d), 3.46-3.45(2H, d), 3.23-3.14(2H, m), 2.85-2.80(2H, e), 1.70-1.68 (3H, t), 1.24-1.23 (3H, d), 1.19-1.17 (3H, d)

Stage 4: (4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid

(4R,5S,6R)-4-nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)- 1-((4-nitrobenzyloxy)carbonyl)-5-((R)-3-((4-nitrobenzyloxy)carbonyl amino)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[ 3,2,0]hept-2-ene-2-carboxylate (1.45 g, 1 mmol) was placed in a Parr shaking vessel and 80 ml THF, 40 ml water and 4.35 g Pd/C were added to it. . The reaction was held for 1.5 hours at a hydrogen pressure of 5 kg. Then, the reaction mixture was filtered through filter paper and washed with ethyl acetate (5×50 ml). The reaction mixture was treated with activated carbon and filtered. The aqueous layer was washed again with ethyl acetate and lyophilized for 2 days to give the final product as a white solid (400 mg, 51.34%).

Compounds of example 299-312 were prepared according to the method in example 298.

Example Structure Analytical data 298

(4R,5S,6R)-6-((R)-1-(2-(1H-тетразол-1-ил)ацетамидо)этил)-3-((3S,5S)-5-((R)-3-аминопирролидин-1-карбонил)пирролидин-3-илтио)-4-метил-7-оксо-1-азабицикло[3,2,0]гепт-2-ен-2-карбоновая кислота

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 3.33-3.40 (m, 1H), 3.67-3.71 (m, 1H), 3.73(m, 1H), 3.78(d, 2H), 3.90(m, 1H), 4.12-4.14(m, 4H), 4.14-4.15 (m, 2H), 4.16 (d, 1H), 4.41 (d, 1H), 4.60 (d, 1H), 4.84 (d, 1H), 5.42 (d, 2H) , 9.27 (s, 1H). mass (533.60) 534.5 299

(4R,5S,6R)-6-((R)-1-(3-amino-3-oxopropanamido)ethyl)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1 -carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.29 (d, 3H), 1.40 (d, 3H), 1.92-1.98 (m, 1H)), 2.04-2.08 (m , 1H), 2.26 (s, 1H), 2.46-2.60 (m, 2H), 2.82 (d, 2H), 3.01 (d, 1H), 3.31-3, 37 (m, 2H), 3.71-3.79 (m, 2H), 4.02-4.07 (m, 2H), 4.35-4.41 (m, 1H), 4.54- 4.58 (m, 1H), 4.60-4.62 (m, 2H), 4.75-4.82 (m, 1H). mass (508.59) 509.2 300

(4R,5S,6R)-6-((R)-1-(2-(1H-1,2,4-triazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5 -(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.23 (d, 3H), 1.33 (d, 3H), 1.92-1.97 (m, 2H), 3.00 (s, 3H), 3 .41-3.42 (s, 3H), 3.50-3.56 (m, 1H), 3.71-3.77 (m, 2H), 4.31-4.39 (m, 2H) , 4.72-4.75(m, 2H), 4.74-4.82(s, 1H), 5.10-5.15(m, 2H), 8.11(s, 1H), 8 .51 (s, 1H). masses (491.56) 492.6. 301

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(2-methyl- 2H-tetrazol-5-yl)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.33 (d, 3H), 1.42 (d, 3H), 1.96-1.99 (m, 1H), 2.99 (s, 3H), 3 .06-3.11 (s, 4H) 3.38-46 (m, 3H), 3.67-3.72 (m, 2H), 3.90-3.99 (m, 2H), 4, 38-4.44 (m, 5H), 4.58.4.61 (m, 1H). mass (506.58) 507.2 302

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(2-methyl-2H-tetrazol-5-yl)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.33 (d, 3H), 1.42 (d, 3H), 1.92 (m, 1H), 2.11-2.25 (m, 1H), 2 .48-2.49 (m, 2H), 3.28-3.49 (m, 2H), 3.51-3.63 (m, 3H), 3.71-3.77 (m, 2H) , 3.87-3.90(m, 3H), 3.92-3.97(m, 4H), 4.06-4.15(m, 2H), 4.73(m, 2H). mass (547.63) 548.4 303

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(pyrazine-2 -carboxamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d,3 H), 1.45 (d, 3H), 2.99-3.02 (s, 3H), 3.04-3.09 (m , 2H), 3.33-3.36 (s, 3H), 3.40-3.42 (m, 2H) 3.65-3.71 (m, 2H), 4.25 (d, 2H) , 4.65-4.72 (m, 2H), 8.74-8.85 (m, 2H), 9.17 (s, 1H). mass (488.56) 489.6 304

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(1-methyl- 1H-tetrazol-5-yl)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.33 (d, 3H), 2.99-3.02 (s, 3H), 3.09-3.11 (m, 4H), 3.34-3.38 (s, 3H), 3.46-3.56 (m, 3H), 3.58-3.65 (m, 2H), 3.74-3.78 ( m, 3H), 4.02 (d, 2H), 4.31-4.38 (m, 1H). mass (506.58) 507.2 305

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-((sulfamoylamino)methyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.35 (d, 3H), 3.32-3.45 (m, 2H), 3.56-3.58 (m, 3H), 3.68-3.73 (m, 3H), 3.95-4.04 (m, 2H), 4.14 (d, 1H), 4.38-4.72 (m, 1H) , 5.41 (d, 2H), 9.26 (s, 1H). mass (529.59) 530.6 306

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(6,7-dihydro-5H-pyrazolo[1,2 -a][1,2,4]triazol-4-y-6-ylthio)-4-methyl-7-oxo-1-azabicyclo[3,2,0]hept-2-en-2-carboxylate ¹ H NMR (D ₂ O) -1.24 (d, 3H), 1.35 (d, 3H), 3.35-3.39 (m, 1H), 3.64-3.65 (m, 2H), 4.22 (d, 2H), 4.43-4.45 (m, 2H), 5.05-5.14 (m, 2H), 5.43 (d, 2H), 9.03 (d, 1H), 9.26 (d, 1H). mass (459.48) 460 307

(4R,5S,6R)-6-((R)-1-(2-(2H-tetrazol-2-yl)acetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine- 3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.35 (d, 3H), 2.97-2.99 (s, 3H), 3.08 (d, 3H), 3 .32-3.38 (m, 2H), 3.55-3.59 (m, 2H), 3.98 (m, 2H), 4.13 (d, 1H), 4.15-4.17 (m, 1H), 4.42 (d, 2H), 5.61-5.63 (m, 2H), 8.85 (s, 1H). mass (492.55) 493.1 308

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(1-methyl-3-( trifluoromethyl)-1H-pyrazole-4-carboxamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.33 (d, 3H), 1.46 (d, 3H), 2.97 (s, 3H), 3.02 (s, 3H), 3.03-3 .04 (m, 2H), 3.09-3.11 (m, 1H), 3.23 (m, 2H), 3.48-3.51 (m, 2H), 3.98-4.01 (m, 5H), 4.53 (m, 1H), 7.95 (s, 1H). mass (558.57) 559.2 309

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(4-(( methylamino)methyl)-1H-1,2,3-triazol-1-yl)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.32 (d, 3H), 1.78 (m, 1H), 2.92-2.94 (m, 2H), 2 .99 (s, 3H), 3.11 (s, 3H), 3.40-3.44 (m, 3H), 3.45-3.48 (m, 2H), 3.57 (m, 2H ), 3.94 (m, 1H), 4.15-4.18 (m, 1H), 4.40 (s, 2H), 4.44-4.46 (m, 1H), 5.32 ( m, 2H), 8.19-8.22 (s, 1H). mass (534.63) 535.6 310

(4R,5S,6R)-3-((3S,5S)-5-((S)-3-(2H-tetrazol-2-yl)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-4- methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.28 (d, 3H), 2.47 (m, 1H), 2.66 (m, 3H), 2.94-3 .11 (m, 2H), 3.22-3.23 (m, 1H), 3.44-3.49 (m, 3H), 3.72 (m, 1H), 3.87 (m, 3H ), 4.03-4.26 (m, 5H), 4.44 (d, 2H), 5.77 (m, 1H), 8.81 (s, 1H). mass (547.63) 548.1 311

(4R,5S,6R)-6-((R)-1-((S)-2-amino-3-(1H-pyrazol-1-yl)propanamido)ethyl)-3-((3S,5S) -5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.11 (d, 3H), 1.13 (d, 3H), 2.99 (s, 3H), 3.08 (s, 3H), 3.50-3 .51 (m, 3H), 3.64-3.75 (m, 3H), 3.97-4.08 (m, 4H), 4.25-4.28 (m, 1H), 4.43 -4.48 (m, 2H), 6.39 (m, 1H), 7.62-7.63 (d, 2H). mass (519.62) 520.4 312

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(5-(( methylamino)methyl)-1H-tetrazol-1-yl)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d. 3H), 1.33 (d, 3H), 2.62 (s, 3H), 3.00 (s, 3H), 3.09 (s , 3H), 3.35-3.40 (m, 3H), 3.59-3.64 (m, 3H), 3.98-4.01 (m, 1H), 4.15-4.17 (d, 1H), 4.35 (m, 2H), 4.42-4.45 (m, 1H), 4.71-4.73 (m, 1H), 5.44 (s, 2H). mass (535.62) 536.2

Preparation of Example 313: (4R,5S,6S)-6-((R)-1-(1H-tetrazol-1-yl)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

Stages 2B and 3B:

Similar to the method described for step 2A and step 3A, (R)-4-nitrobenzyl 4-((2R,3S)-3-((R)-1-(2H-tetrazol-2-yl)ethyl)-4- oxoazetidin-2-yl)-2-diazo-3-oxopentanoate (600 mg) in (4R,5S,6S)-4-nitrobenzyl 6-((R)-1-(2H-tetrazol-2-yl)ethyl) -3-((3S,5S)-5-(dimethylcarbamoyl)-1-((4-nitrobenzyloxy)carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0 ]hept-2-ene-2-carboxylate was converted to its enol phosphate (0.28 g, 39.9%) and then finally to the title product (270 mg, 27%). ¹ H NMR: 9.53 (1H, s), 8.21-8.26 (4H, m), 7.71 (2H, m), 7.64-7.62 (1H, m), 7, 53-7.51 (1H, d), 5.47-5.43 (1H, m), 5.29-5.20 (2H, m), 5.06-5.02 (2H, m), 4.83-4.72(1H, m), 4.26-4.21(1H, m), 4.12-4.08(1H, m), 4.01-4.00(1H, m ), 3.85-3.81(1H, m), 3.59-3.53(1H, m), 3.18-3.12(1H, m), 3.01-2.95(3H , d), 2.86 (3H, d), 2.80 (1H, m), 1.70 (3H, d), 1.62-1.60 (1H, m), 1.14 (3H, e).

Step 4B: (4R,5S,6S)-6-((R)-1-(2H-tetrazol-2-yl)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)-pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

(4R,5S,6S)-4-nitrobenzyl 6-((R)-1-(2H-tetrazol-2-yl)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)-1-( (4-Nitrobenzyloxy)carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate (270 mg) was converted to the title compound the product above, following a method similar to that described for step 4A (100 mg, 67%).

Example Structure Analytical data 313

(4R,5S,6S)-6-((R)-1-(2H-тетразол-2-ил)этил)-3-((3S,5S)-5-(диметилкарбамоил)пирролидин-3-илтио)-4-метил-7-оксо-1-азабицикло[3,2,0]гепт-2-ен-2-карбоновая кислота

(4R,5S,6S)-6-((R)-1-(2H-tetrazol-2-yl)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.84 (d, 3H), 2.99 (s, 3H), 3.06 (s, 3H), 3.27-3 .31 (m, 2H), 3.37-3.40 (m, 1H), 3.63-3.67 (m, 1H), 3.8 (m, 1H), 4.10 (d, 1H ), 4.20 (d, 1H), 4.68 (m, 2H), 5.59-5.63 (m, 1H), 8.82 (s, 1H). mass (435.50) 436.1 314

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(piperazine-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.26 (d, 3H), 1.34 (d, 3H), 1.85-1.92 (m, 1H), 2.94-3.26 (m, 2H), 3.46-3.49(m, 4H), 3.57-3.58(m, 2H), 3.62-3.72(m, 1H), 3.73-3.76( m, 1H), 3.80-3.84 (m, 2H), 3.87-3.92 (m, 1H), 3.94-4.13 (m, 1H), 4.30 (d, 1H), 4.43-4.49(m, 1H), 4.51-4.53(m, 1H), 5.47(m, 2H), 9.27(s, 1H). mass (533.60) 534.6 315

(4R,5S,6R)-6-((R)-1-(2-(5-amino-2H-tetrazol-2-yl)acetamido)ethyl)-3-((3S,5S)-5-( dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.89-1.92 (m, 1H), 2.99 (s, 3H), 3 .07 (s, 3H), 3.32-3.36 (m, 2H), 3.56 (d, 1H), 3.66 (m, 1H), 3.98 (m, 1H), 4, 14 (d, 1H), 4.40-4.42 (m, 1H), 4.60-4.62 (m, 2H), 5.34 (d, 2H). mass (507.57) 508.2 316

(4R,5S,6R)-6-((R)-1-(2-(5-amino-2H-tetrazol-2-yl)acetamido)ethyl)-3-((3S,5S)-5-( (R)-3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.80-1.85 (m, 1H), 2.08-2.30 (m, 2H), 2.44-2.48 (m, 2H), 2.70-3.00 (m, 3H), 3.19 (d, 3H), 3.29-3.57 (m, 3H) , 3.54-3.78(m, 2H), 4.14(d, 1H), 4.38-4.42(m, 1H), 5.29-5.32(m, 1H). mass (548.62) 549.1 317

(4R,5S,6R)-6-((R)-1-(2-(5-amino-3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)acetamido)ethyl)- 3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept -2-en-2-carboxylic acid ¹ H NMR (D2O) -1.12 (d, 3H), 1.33 (d, 3H), 2.25-2.26 (m, 2H), 2.48-2.50 (m, 1H) , 2.60-2.67 (m, 1H), 2.8-3.00 (m, 1H), 3.34 (d, 2H), 3.55 (d, 2H), 3.65 (d , 2H), 3.76 (d, 2H), 3.88 (d, 2H), 3.94 (d, 1H), 4.13-4.15 (m, 1H), 4.41-4, 57 (m, 2H). mass (615.63) 616.1 318

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-methyl-2-( 1H-tetrazol-1-yl)propanamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.15 (d, 3H), 1.35 (d, 3H), 1.88-1.93 (s, 6H), 3.01 (s, 3H), 3 .07 (s, 3H), 3.34-3.40 (m, 2H), 3.49 (d, 2H), 3.63-3.64 (m, 2H), 4.00-4.17 (m, 2H), 4.37-4.41 (m, 1H), 4.67-4.71 (m, 1H), 9.36 (s, 1H). mass-(520.61) 521

Preparation of Example 319: (4R,5S,6S)-6-((R)-1-(1H-tetrazol-1-yl)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

Stage 1: (R)-4-nitrobenzyl 4-((2R,3S)-3-((R)-1-(1H-tetrazol-1-yl)ethyl)-4-oxoazetidin-2-yl)-2 -diazo-3-oxopentanoate (A) and (R)-4-nitrobenzyl 4-((2R,3S)-3-((R)-1-(2H-tetrazol-2-yl)ethyl)-4-oxoazetidine -2-yl)-2-diazo-3-oxopentanoate (B)

To a solution of (R)-4-nitrobenzyl 2-diazo-4-((2R,3S)-3-((S)-1-hydroxyethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate (900 mg, 2.307 mmol) were added triphenylphosphine (967 mg, 3.691 mmol) and tetrazole (193 mg, 2.768 mmol) in tetrahydrofuran (9 ml). Then, diisopropyl azodicarboxylate (746 mg, 3.691 mmol) at 0°C was added to the reaction mixture and warmed to room temperature and stirred for 10 hours. After completion of the reaction, the reaction mixture was quenched with water and the crude product was extracted with ethyl acetate. The organic layer was evaporated to give a crude product which was purified by column chromatography to give products A (300 mg, 29.3%) and B (480 mg, 47%). ¹ H NMR: Product A: (DMSO-d ₆ , 400 MHz): 9.36 (s, 1H), 8.50 (s, 1H), 8.27-8.25 (d, 2H), 8, 28-7.70 (d, 2H), 5.43 (s, 2H), 5.16-5.12 (t, 1H) 3.54 (s, 2H), 3.45-3.42 (d , 1H), 1.59-1.57 (d, 3H), 0.98-0.96 (d, 3H). Product B: (DMSO-d ₆ , 400 MHz): 8.95 (s, 1H), 8.48 (s, 1H), 8.27-8.25 (d, 2H), 5.43 (s, 2H), 3.56-3.47 (m, 2H), 1.61-1.59 (d, 3H), 0.96-0.95 (d, 3H).

Step 2A: (4R,5R,6S)-4-nitrobenzyl 6-((R)-1-(1H-tetrazol-1-yl)ethyl)-3-(diphenoxyphosphoryloxy)-4-methyl-7-oxo-1 -azabicyclo[3,2,0]hept-2-ene-2-carboxylate

(R)-4-nitrobenzyl 4-((2R,3S)-3-((R)-1-(2H-tetrazol-2-yl)ethyl)-4-oxoazetidin-2-yl)-2-diazo- 3-oxopentanoate (530 mg, 1.19 mmol) was taken up in 30 ml of acetone under N ₂ atmosphere. Rhodium octanoate (0.025 g, 0.0324 mmol) was added to this solution, and the resulting reaction mixture was heated at 65-70° C. for 1.5 hours. After completion of the reaction, the reaction mixture was cooled to -40°C, followed by the addition of diphenyl chlorophosphate (0.4 ml, 1.93 mmol), diisopropylethylamine (0.35 ml, 2 mmol) and a catalytic amount of dimethylaminopyridine. The reaction mixture was brought to -20°C and stirred for 1 hour. At -20°C, diisopropylethylamine (0.35 ml) was added to the reaction mixture and quenched with water and extracted with dichloromethane. Then, the organic layer was dried over sodium sulfate and concentrated in vacuo at room temperature to give the crude product. This crude product was purified by column chromatography to give the product as a solid (250 mg, 32.2%).

Step 3A: (4R,5S,6S)-4-nitrobenzyl 6-((R)-1-(1H-tetrazol-1-yl)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)- 1-((4-nitrobenzyloxy)carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate

The product (0.25 g, 0.39 mmol) obtained in step 2A was taken up in 10 ml of acetonitrile and cooled to 0° C. and degassed for 10 minutes. Thiol (0.22 g, 0.39 mmol) was added to this reaction mixture, followed by the addition of diisopropylethylamine (0.1 ml, 0.57 mmol) under N ₂ atmosphere. The reaction mixture was again degassed for 10-15 minutes. The reaction mixture was further stirred at 0° C. for 2 hours. After completion of the reaction, the reaction mixture was diluted with water and extracted using ethyl acetate. The organic layer was concentrated and the resulting crude mixture was purified by column chromatography to give the product (260 mg, 33.6%). ¹ H NMR: (DMSO-d ₆ , 400 MHz): 9.05 (1H, s), 8.26-8.21 (4H, m), 7.72-7.51 (4H, m), 5 .65-5.61(1H, q), 5.47-5.06(4H, m), 4.81-4.72(1H, m), 4.06-4.05(1H, m) , 3.83-3.81(2H, m), 3.58-3.56(2H, m), 3.10(1H, m), 3.02-2.95(3H, d), 2 .81(3H, d), 2.80(1H, m), 1.73-1.71(3H, d), 1.60(1H, m), 1.18-1.16(3H, d ).

Step 4A: (4R,5S,6S)-6-((R)-1-(1H-tetrazol-1-yl)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3- ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

(4R,5S,6S)-4-nitrobenzyl 6-((R)-1-(1H-tetrazol-1-yl)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)-1-( (4-nitrobenzyloxy)carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (250 mg, 0.33 mmol) hydrogenated using Pd/C (500 mg) in a mixture of THF-H ₂ O (20 ml:10 ml) for 1.5 hours at a hydrogen pressure of 5 kg. After standard workup, the title compound was obtained (70 mg, 49%).

Examples 326-328 were prepared following the method described in Preparations 313 and 319 using suitably substituted tetrazoles.

Example 328 was prepared by reacting the compound obtained in Step 2A with the appropriate R ₁ -SH group, followed by the method of Steps 3A and 4A or Example 319.

Examples 334 and 335 were prepared by reacting the compound obtained in step 2 with the appropriate R1-SH group, followed by the method of step 3 of example 347.

Example Structure Analytical data 319

(4R,5S,6S)-6-((R)-1-(1H-тетразол-1-ил)этил)-3-((3S,5S)-5-(диметилкарбамоил)пирролидин-3-илтио)-4-метил-7-оксо-1-азабицикло[3,2,0]гепт-2-ен-2-карбоновая кислота

(4R,5S,6S)-6-((R)-1-(1H-tetrazol-1-yl)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.81 (d, 3H), 2.99 (s, 3H), 3.06 (d, 3H), 3.31 (d , 1H), 3.35-3.40 (m, 1H), 3.61-3.66 (m, 2H), 3.99 (d, 1H), 4.03-4.06 (m, 1H ), 4.20-.4.23 (m, 1H), 4.67-4.71 (m, 2H), 5.39-5.42 (m, 1H), 9.34 (s, 1H) . mass (435.50) 436 320

(4R,5S,6R)-6-((R)-1-(2-(5-amino-3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)acetamido)ethyl)- 3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.33 (d, 3H), 1.19 (d, 3H), 2.99-3.00 (s, 3H), 3.04 (d, 1H), 3 .09 (d, 3H), 3.30-3.34 (m, 1H), 3.42-3.47 (m, 1H), 3.55-3.58 (m, 1H), 3.69 -3.74(m, 1H), 4.01-4.04(m, 1H), 4.13-4.16(m, 1H), 4.39-4.43(m, 1H), 4 .75-.477 (m, 3H), 4.8-4.87 (m, 1H). mass (574.58) 575.1 321

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(1-methyl- 1H-tetrazol-5-ylthio)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.12 (d, 3H), 1.29 (d, 3H), 3.00 (s, 3H), 3.08 (s, 3H), 3.10-3 .14 (m, 1H), 3.20-3.24 (m, 1H), 3.43-3.48 (m, 1H), 3.49-3.51 (m, 2H), 3.80 -3.85(m, 2H), 3.92-3.94(m, 2H), 4.03-4.12(m, 4H), 4.32-4.36(m, 1H), 4 .81-4.84 (m, 1H). mass (538.64) 539.5 322

(4R,5S,6R)-6-((R)-1-((S)-2-amino-3-(1H-tetrazol-1-yl)propanamido)ethyl)-3-((3S,5S) -5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.65 (d, 3H), 1.20 (d, 3H), 2.4-2.6 (m, 1H), 3.00 (s, 3H), 3 .07-3.08 (s, 3H), 3.22-3.36 (m, 2H), 3.45 (d, 2H), 3.74-3.77 (m, 1H), 3.99 -4.04(m, 3H), 4.28-4.32(m, 1H), 4.70-4.82(m, 3H), 9.24(s, 1H). mass (521.59) 522.3 323

(4R,5S,6R)-6-((R)-1-((S)-2-amino-3-(2H-tetrazol-2-yl)propanamido)ethyl)-3-((3S,5S) -5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.15 (d, 3H), 1.20 (d, 3H), 2.40-2.46 (m, 1H), 2.99 (s, 3H), 3 .07-3.09 (s, 3H), 3.33-3.42 (m, 3H), 3.50 (d, 1H), 3.63-3.67 (m, 2H), 4.04 -4.09 (m, 3H), 4.27-4.30 (m, 1H), 4.65-4.74 (m, 1H), 4.94-5.04 (m, 1H), 8 .81 (s, 1H). mass (521.59) 522.5 324

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((S)- 3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 3.23-3.26 (m, 1H), 3.31-3.36 (m, 1H), 3.45-3.48 (m, 1H), 3.58 (d, 1H), 3.67-3.79 (m, 2H), 3.83 (d, 2H), 3.93 -4.04 (m, 4H), 4.14 (d, 2H), 4.32-4.38 (m, 3H), 5.40-5.47 (m, 2H), 9.25 (s , 1H). mass (533.60) 534 325

(4R,5S,6R)-6-((R)-1-((Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido)ethyl)-3-((3S, 5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.37 (d, 3H), 1.82 (d, 1H), 2.98 (d, 3H), 3.08 (d , 3H), 3.29-3.33 (m, 2H), 3.49 (d, 2H), 3.60 (d, 1H), 3.98 (s, 3H), 4.20-4, 23 (m, 1H), 4.52-4.54 (m, 2H), 4.55 (d, 1H), 8.9 (s, 1H). mass (565.67) 566.2 326

(4R,5S,6S)-6-((R)-1-(5-amino-2H-tetrazol-2-yl)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.75 (d, 3H), 2.99 (s, 3H), 3.06-3.09 (s, 3H), 3 .27-3.31(m, 2H), 3.36(d, 1H), 3.61-3.64(m, 1H), 3.94(d, 2H), 4.16(d, 1H ), 4.17-4.20 (m, 2H), 5.33 (d, 1H). mass (450.52) 451 327

(4R,5S,6S)-6-((R)-1-(5-amino-2H-tetrazol-2-yl)ethyl)-3-((3S,5S)-5-((R)-3 -aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.75 (d, 3H), 2.14 (d, 1H), 2.39-2.51 (m, 2H), 2 .89-2.92 (m, 1H), 3.25-3.31 (m, 2H), 3.44-3.48 (m, 1H), 3.50-3.59 (m, 1H) , 3.71-3.77 (m, 4H), 3.86-3.88 (m, 1H), 3.90-3.98 (m, 1H), 4.04 (d, 1H, 4, 14 (d, 1H), 5.31-5.35 (m, 1H), wt (491.57) 492.5 328

(4R,5S,6S)-6-((R)-1-(1H-tetrazol-1-yl)ethyl)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1 -carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.77 (d, 3H), 2.00-2.25 (m, 2H), 2.45-2.49 (m, 2H), 2.88-3.00 (m, 1H), 3.23-3.33 (m, 1H), 3.44-3.47 (m, 1H), 3.60 (d, 1H) , 3.69-3.77 (m, 3H), 3.86-3.91 (m, 2H), 4.03-4.10 (m, 2H), 4.20-4.22 (m, 1H), 4.38 (m, 1H), 5.39-5.42 (m, 1H). mass (476.55) 477.2 329

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3R,4R )-3-amino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.88-1.92 (m, 1H), 2.92-2.97 (m, 1H), 3.27-3.37(m, 2H), 3.51-3.57(m, 3H), 3.59-3.70(m, 3H), 3.78-3.95( m, 3H), 4.15(d, 1H), 4.35-4.46(m, 3H), 5.38-5.47(m, 2H). mass (549.60) 550.5 330

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-(5-methyl- 1H-tetrazol-1-yl)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.35 (d, 3H), 1.86-1.93 (m, 1H), 2.60 (s, 3H), 2 .99 (s, 3H), 3.09 (s, 3H), 3.3-3.40 (m, 2H), 3.58-3.65 (m, 2H), 3.98-4.01 (m, 2H), 4.16 (d, 1H), 4.40-4.44 (m, 1H), 4.64-4.68 (m, 1H), 5.31 (s, 2H). mass (506.58) 507.2 331

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(2-(5-methyl-1H-tetrazol-1-yl)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.34 (d, 3H), 1.87 (m, 1H), 2.24 (dd, 1H), 2.23 (m , 1H), 2.57 (s, 3H), 2.87 (m, 1H), 3.22 (m, 1H), 3.24 (m, 2H), 3.36 (m, 2H), 3 .58 (m, 2H), 3.85 (dd, 2H), 3.91 (dd, 1H), 4.04 (d, 1H), 4.30 (m, 1H), 4.42 (t, 1H), 5.03 (s, 3H). mass (547.63) 548.1 332

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-amino- 4-methylpiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.03 (d, 3H), 1.27 (d, 3H), 1.50 (s, 3H), 1.85-1.99 (m, 2H), 3 .26 (m, 1H), 3.33 (d, 1H), 3.57 (d, 1H), 3.59 (m, 3H), 3.79 (m, 4H), 3.98 (m, 1H), 4.40 (m, 4H), 4.43 (d, 1H), 4.63 (t, 1H), 5.44 (d, 2H), 9.27 (s, 1H). mass (561.66) 562.5 333

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(6-amino- 3-azabicyclo[3.1.0]hexane-3-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.35 (d, 3H), 1.80 (m, 1H), 1.92 (m, 2H), 2.12 (dd , 2H), 2.47(m, 1H), 2.84(m, 1H), 3.30-3.32(m, 2H), 3.56(d, 2H), 3.56-3, 63 (d, 2H), 3.62-3.89 (m, 3H), 4.19 (d, 1H), 4.42 (dd, 1H), 5.43 (m, 2H), 9.27 (d, 1H). mass (545.61) 546.1 334

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-(2-(5-(trifluoromethyl)-2H-tetrazol-2-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.37 (d, 3H), 2.23 (m, 1H), 2.49 (m, 2H), 2.90 (m , 1H), 3.24 (t, 1H), 3.44-3.35 (m, 2H), 3.59 (m, 2H), 3.76-3.68 (m, 2H), 3, 86-3.91(m, 2H), 4.04(m, 1H), 4.15(d, 1H), 4.26-4.33(dd, 1H), 4.44(m, 1H) , 5.76 (t, 2H). mass (601.60) 602.3 335

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(2-( 5-(trifluoromethyl)-2H-tetrazol-2-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.37 (d, 3H), 1.98 (m, 1H), 1.98 (m, 1H), 2.98-3 .00 (m, 1H), 3.04 (s, 3H), 3.08 (s, 3H), 3.34-3.41 (m, 2H), 3.68 (dd, 2H), 4, 01 (t, 1H), 4.18 (d, 1H), 4.42 (t, 1H), 4.68 (t, 1H), 5.73 (s, 2H). mass (560.55) 561.1 336

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-aminopiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.35 (d, 3H), 1.57 (m, 1H), 1.79 (m, 2H), 1.92 (m , 1H), 2.17 (m, 1H), 3.27 (m, 1H), 3.42 (m, 2H), 3.44 (m, 3H), 3.58 (d, 2H), 3 .65 (m, 2H), 3.94 (m, 1H), 4.16 (d, 2H), 4.42 (dd, 2H), 5.43 (d, 2H), 9.28 (s, 1H). mass (547.63) 548.2 337

(4S,5S,6R)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4- methyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.38 (d, 3H), 1.90 (m, 2H), 2.99 (s, 3H), 3.04 (m , 1H), 3.09 (s, 3H), 3.36 (m, 2H), 3.62 (m, 2H), 4.01 (m, 1H), 4.18 (d, 1H), 4 .46 (t, 1H), 4.65 (m, 1H), 6.16 (t, 1H). mass (460.50) 461.1 338

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-(5-(ethoxycarbonyl)-1H- tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.37 (d, 3H), 1.40-1.44 (m, 3H), 1.82-1.84 (m, 1H), 1.87 (m, 1H), 2.99 (s, 3H), 3.09 (s, 3H), 3.37 (m, 2H), 3.55 (m, 2H), 3, 98 (m, 1H), 4.17 (m, 1H), 4.41 (m, 1H), 4.57 (m, 3H), 5.65 (d, 2H). mass (564.61) 565.5 339

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-(ethoxycarbonyl)-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.23 (d, 3H), 1.32 (d, 3H), 1.42 (m, 3H), 2.12 (m, 1H), 2.24 (m , 1H), 2.49 (m, 1H), 2.90 (m, 1H), 3.34 (m, 1H), 3.37-3.39 (m, 2H), 3.57-3, 60 (m, 2H), 3.70-3.75 (m, 2H), 3.88 (m, 2H), 4.07 (m, 1H), 4.29 (m, 1H), 4.35 (m, 2H), 4.52 (m, 2H), 5.65 (d, 2H). mass (605.67) 606.1 340

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-aminopiperidine- 1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.33 (d. 3H), 1.57-1.60 (m, 2H), 1.84 (m, 1H), 2 .17 (m, 2H), 2.93 (m, 2H), 3.29-3.37 (m, 3H), 3.50-3.58 (m, 3H), 3.96 (m, 2H ), 4.16 (d, 1H), 4.42 (m, 1H), 4.48-4.57 (m, 2H), 5.44 (d, 2H), 9.28 (s, 1H) . mass (547.63) 548.2 341

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((S)- 3-aminopiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.32 (d, 3H), 1.66-1.8 (m, 2H), 1.92 (s, 3H), 2 .90-2.93 (m, 1H), 3.13-3.19 (m, 1H), 3.27-3.43 (m, 3H), 3.45-3.50 (m, 2H) , 3.56 (d, 1H), 3.70-3.73 (m, 1H), 3.93 (d, 1H), 4.15 (d, 1H), 4.36-4.47 (m , 2H), 4.50-4.80 (m, 1H), 5.38-5.48 (m, 2H), 9.27 (s, 1H). mass (547.63) 548.2 342

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(3 -aminoazetidin-1-yl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.76-1.81 (m, 1H), 1.91 (m, 1H), 2 .83-2.89 (m, 2H), 2.99-3.02 (m, 2H), 3.19-3.35 (m, 3H), 3.45-3.49 (m, 3H) , 3.58 (m, 3H), 3.87-3.97 (m, 3H), 4.04 (d, 2H), 4.14 (d, 1H), 4.40-4.43 (m , 2H), 4.47-4.54 (m, 1H), 5.43 (d, 2H), 9.27 (s, 1H). mass (602.71) 603.2. 343

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(3 -(aminomethyl)azetidin-1-yl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.26 (d, 3H), 1.32 (d, 3H), 1.81 (m, 1H), 1.91 (m, 1H), 2.00 (m , 3H), 2.81-2.90 (m, 3H), 3.02 (d, 2H), 3.18-3.35 (m, 5H), 3.48-3.57 (m, 4H ), 3.87-3.95 (3H), 4.14 (d, 1H), 4.42-4.53 (m, 3H), 5.43 (d, 2H), 9.27 (s, 1H) C ₂₇ H ₄₀ N ₁₀ O ₅ S; HPLC-96.6%; mass (616.74) 617.2 344

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-(aminomethyl )-3-fluoroazetidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.32 (d, 3H), 1.80-1.82 (m, 1H), 1.92 (m, 1H), 2 .74 (m, 1H), 3.12 (m, 1H), 3.35 (d, 2H), 3.54 (d, 2H), 3.74-3.85 (m, 2H), 4, 04-4.15 (m, 1H), 4.32 (d, 2H), 4.42 (m, 1H), 4.56 (d, 2H), 5.44 (d, 2H), 9.27 (s, 1H). mass (551.59) 552.1 345

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((1R,5S ,8S)-8-amino-3-azabicyclo[3.2.1]octane-3-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept -2-en-2-carboxylic acid ¹ H NMR (D ₂ O)-1.21 (d, 3H), 1.37 (d, 3H), 1.60-(m, 1H), 1.73-1.79 (m, 1H), 1.91 (m, 2H), 2.23 (m, 2H), 2.52 (d, 3H), 3.20-3.22 (m, 3H), 3.52-3.64 (m, 6H), 3.75 (m, 1H), 3.77-4.13 (m, 3H), 4.22-4.51 (m, 1H), 5.44 (d, 2H), 9.27 (s, 1H). mass (573.67) 574.2 346

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(aminomethyl )-4-fluoropiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.29 (d, 3H), 1.64 (d, 3H), 1.80 (m, 2H), 2.23 (m, 3H), 2.56 (m , 2H), 2.92 (m, 2H), 3.25-3.30 (m, 2H), 3.59 (m, 3H), 3.75 (m, 2H), 3.96 (m, 1H), 4.42 (m, 2H), 5.43 (m, 3H), 9.28 (s, 1H). Wt (579.65) 580.

Preparation of Example 347 ((4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo -6-((R)-1-(2-(5-(trifluoromethyl)-1H-tetrazol-1-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid)

Getting C:

Step (i): Ethyl 2-(2,2,2-trifluoroacetamido)acetate

Ethyl trifluoroacetate (10.7 g, 0.075 mol) was dissolved in methanol (ml) and cooled to 0°C. Glycine ester hydrochloride (10.5 g, 0.075 mol) was added to this solution and the reaction mixture was stirred for 5 minutes. Triethylamine (15.7 ml, 0.112 mol) was added dropwise at 0° C. and stirred for 15 minutes. Then, the reaction mixture was brought to room temperature and stirred overnight. The solvent of the reaction mixture was evaporated in vacuo, and water was added to the crude residue, followed by extraction with ethyl acetate. Then, the organic layer was washed with water, brine, dried over sodium sulfate and concentrated to give the crude product (15 g). NMR: (CDCl ₃ , 400 MHz): 6.85 (s, 1H), 4.25-4.30 (m, 2H), 4.12-4.15 (m, 2H), 1.30-1 .33 (m, 3H).

Step (ii): Ethyl 2-(2,2,2-trifluoroethanethioamido)acetate

Ethyl 2-(2,2,2-trifluoroacetamido)acetate (15 g, 0.0753 mol) was dissolved in toluene (20 ml) and cooled to 0°C. Solid NaHCO ₃ was added to the reaction mixture and stirred for 5 minutes. P ₂ S ₅ (10 g, 0.045 mmol, 0.6 eq.) was added very slowly in portions and stirred for 10 minutes at 0°C. Then, the reaction mixture was heated at 70°C for 6 hours. After completion of the reaction, the reaction mixture was brought to room temperature and quenched slowly with water at 0°C and was extracted with ethyl acetate. The organic layer was washed with 5% NaHCO ₃ solution, water and brine, respectively, and dried over sodium sulfate. Then, the crude reaction mixture was concentrated in vacuo and the product was isolated by column chromatography (11 g, 67.8%). ¹ H NMR: (CDCl3, 400 MHz): 8.46 (s, 1H), 4.29-4.38 (m, 2H), 4.12-4.15 (m, 2H), 1.30- 1.35 (m, 3H).

Step (iii): Ethyl 2-(5-(trifluoromethyl)-1H-tetrazol-1-yl)acetate

Ethyl 2-(2,2,2-trifluoroethanethioamido)acetate (11 g, 0.051 mol) was dissolved in dichloromethane (110 ml) at ambient temperature. Azidotrimethylsilane (13.5 ml, 0.102 mol) was added dropwise to this solution and stirred for 10 minutes. A solution of SnCl ₄ (13.3 ml, 0.127 mmol) in dichloromethane (ml) was added dropwise and stirred for 15 minutes. Then, the reaction mixture was stirred overnight at room temperature. Then, the reaction mixture was slowly quenched with a saturated solution of NaHCO ₃ at 0°C, filtered through a Celite pad, washed with dichloromethane. Then, the organic layer was separated, washed with water, brine, dried over sodium sulfate and concentrated in vacuo to give the crude product. Then, the crude product was purified by column chromatography to give the product (6 g, 52.6%). ¹ H NMR (DMSO-d ₆ , 400 MHz): 5.83 (s, 2H), 4.20-4.26 (m, 2H), 1.18-1.23 (m, 3H).

Step (iv): 2-(5-(Trifluoromethyl)-1H-tetrazol-1-yl)acetic acid

2-(5-(Trifluoromethyl)-1H-tetrazol-1-yl)acetic acid (7.3 g, 0.033 mol) was dissolved in THF (70 ml). LiOH solution ^. H ₂ O (1.5 g, 0.036 mol) in water (80 ml) was added dropwise at room temperature and the resulting reaction mixture was stirred for 2 hours. After completion of the reaction, the solvent was evaporated in vacuo and the resulting crude residue was dissolved in water. The aqueous layer was washed with ethyl acetate and then acidified with 2N HCl and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulfate and concentrated in vacuo to give the desired product (5.6 g, 87.6%). ¹ H NMR (DMSO-d ₆₄₀₀ MHz): 14.00 (br s, 1H), 5.69 (s, 2H).

Preparation of Example 347 6-((R)-1-(2-(5-(trifluoromethyl)-1H-tetrazol-1-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid

Stage 1: (R)-4-Nitrobenzyl2-diazo-3-oxo-4-((2R,3R)-4-oxo-3-((R)-1-(2-(5-(trifluoromethyl)-1H -tetrazol-1-yl)acetamido)ethyl)azetidin-2-yl)pentanoate

5-Trifluorotetrazolacetic acid (2.1 g, 0.011 mol) was dissolved in ethyl acetate (ml), cooled to 0°C, and TBTU (4.47 g, 0.014 mol) was added to this solution and stirred for 5 minutes at the same temperature. Diisopropylethylamine (3.8 ml, 0.022 mol) was added dropwise and stirred for 10 minutes at 0°C. Then, the reaction mixture was brought to room temperature and further stirred for 1 hour. The reaction mixture was again cooled to 0°C, and a solution of trifluoroacetate salt of (R)-4-nitrobenzyl 4-((2R,3R)-3-((R)-1-aminoethyl)-4-oxoazetidine-2- yl)-2-diazo-3-oxopentanoate (3.7 g, 0.007 mol) in ethyl acetate (25 ml), followed by dropwise addition of diisopropylethylamine (3.8 ml) and stirring for 10 minutes at 0°C. Then, the reaction mixture was brought to room temperature and stirred overnight. After completion of the reaction, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water followed by brine, dried over sodium sulfate and concentrated in vacuo to give a crude residue which was then purified by column chromatography to give the product (1 g, 23.9%). ¹ H NMR (CDCl ₃ , 400 MHz): 1.19-1.21 (3H, d), 1.35-1.37 (3H, d), 2.86-2.88 (1H, m), 3.58-3.69(2H, m), 4.24-4.33(1H, m), 5.22-5.29(2H, m), 5.35(2H, s), 6, 04 (1H, s), 6.71-6.73 (1H, d), 7.53-7.55 (2H, d), 8.25-8.28 (2H, d).

Stage 2: (4R,5R,6R)-4-nitrobenzyl 3-(diphenoxyphosphoryloxy)-4-methyl-7-oxo-6-((R)-1-(2-(5-(trifluoromethyl)-1H-tetrazole -1-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate

(R)-4-nitrobenzyl 2-diazo-3-oxo-4-((2R,3R)-4-oxo-3-((R)-1-(2-(5-(trifluoromethyl)-1H-tetrazole -1-yl)acetamido)ethyl)azetidin-2-yl)pentanoate (1.1 g, 1.94 mmol) was dissolved in 50 ml of acetone under N ₂ atmosphere. Rhodium octanoate (40 mg, 0.051 mmol) was added to this solution and heated at 70° C. for 1 hour. Then, the reaction mixture was cooled to -40° C. and diphenyl chlorophosphate (0.64 ml, 3.1 mmol), diisopropylethylamine (0.6 ml, 3.44 mmol) and a catalytic amount of dimethylaminopyridine were added successively. Then, the reaction mixture was stirred for 1 hour at -20°C. Diisopropylethylamine (0.6 ml) was again added to the reaction mixture and quenched with water. The aqueous layer was extracted with dichloromethane and the organic layer was evaporated in vacuo at room temperature. The oil thus obtained was purified by column chromatography to give the product as a solid residue (850 mg).

Step 3: (4R,5S,6R)-4-Nitrobenzyl 4-methyl-3-((3S,5S)-1-((4-nitrobenzyloxy)carbonyl)-5-((R)-3-((4 -nitrobenzyloxy)carbonylamino)pyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-6-((R)-1-(2-(5-(trifluoromethyl)-1H-tetrazol-1-yl)acetamido )ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate

(4R,5R,6R)-4-Nitrobenzyl 3-(diphenoxyphosphoryloxy)-4-methyl-7-oxo-6-((R)-1-(2-(5-(trifluoromethyl)-1H-tetrazole-1- yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (500 mg, 0.65 mmol) was dissolved in acetonitrile (10 ml) at 0°C. Then, the solution was degassed for 10 minutes using N ₂ atmosphere. To this solution was added thiol (0.372 g, 0.65 mmol) at 0° C. under N ₂ , followed by the addition of diisopropylethylamine (0.2 ml, 1.15 mmol). The resulting solution was degassed again for 15 minutes. The reaction mixture was stirred under N ₂ at 0° C. for 2 hours. After completion of the reaction, the reaction mixture was quenched using water and extracted with ethyl acetate. Then, the organic layer was washed with water, brine, dried over sodium sulfate and evaporated in vacuo to give a crude residue. The crude reaction mixture was purified by column chromatography to give the product (450 mg, 64%) as a solid residue. ¹ H NMR (DMSO-d ₆ , 400 MHz): 1.18-1.19 (3H, d), 1.22-1.24 (3H, d), 1.73 (2H, m), 2, 83(1H, m), 3.14-3.17(2H, m), 3.47-3.69(4H, m), 3.88-3.90(2H, m), 4.12- 4.22(4H, m), 4.54(1H, m), 5.07-5.09(1H, m), 5.17-5.2(3H, m), 5.41-5, 44(1H, d), 5.48-5.52(3H, m), 7.47-7.49(2H, m), 7.52-7.54(2H, m), 7.60- 7.62(3H, m), 7.70-7.72(1H, m), 8.20-8.24(6H, m), 8.75-8.77(1H, d).

Example 348 was prepared by reacting the compound obtained in step 2 with the appropriate R ¹ -SH group, followed by the method of step 3 of example 347.

Example Structure Analytical data 347

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-аминопирролидин-1-карбонил)пирролидин-3-илтио)-4-метил-7-оксо-6-((R)-1-(2-(5-(трифторметил)-1H-тетразол-1-ил)ацетамидо)этил)-1-азабицикло[3,2,0]гепт-2-ен-2-карбоновая кислота

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-(2-(5-(trifluoromethyl)-1H-tetrazol-1-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.27 (d, 3H), 1.36 (d, 3H), 1.86 (m, 1H), 2.49 (d, 1H), 2.89 (m , 2H), 3.43 (m, 2H), 3.58 (m, 2H), 3.62 (d, 2H), 3.73 (d, 2H), 4.06 (d, 2H), 4 .16 (d, 1H), 4.28-4.42 (m, 2H), 5.62 (m, 2H). mass (601.60) 602.5 348

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(2-( 5-(trifluoromethyl)-1H-tetrazol-1-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O)-1,22-(d, 3H), 1.36 (d, 3H), 1.86 (m, 1H), 3.07 (s, 3H), 3.12 ( s, 3H), 3.37 (d, 3H), 3.59 (m, 2H), 3.98 (m, 1H), 4.86 (d, 1H), 4.41 (m, 1H), 4.61 (m, 1H), 5.61 (s, 2H). mass (560.55) 561.1 349

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-(difluoromethyl)-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.35 (d, 3H), 1.92 (m, 1H), 1.92-2.38 (m, 1H) 2, 40-2.49 (m, 2H), 2.89-2.96 (m, 2H), 3.23-3.34 (m, 2H), 3.47 (m, 1H), 3.57 ( m, 2H), 4.06 (m, 2H), 4.13-4.15 (m, 2H), 4.40-4.80 (m, 2H), 5.55 (s, 2H), 7 .46 (t, 1H). mass (583.61) 584.2 350

(4R,5S,6R)-6-((R)-1-(2-(5-(difluoromethyl)-1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5 -(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.36 (d, 3H), 1.84-1.89 (m, 1H), 3.03 (s, 3H), 3 .07 (s, 3H), 3.33-3.38 (m, 2H), 3.56-3.62 (m, 2H), 3.99 (m, 2H), 4.16 (d, 1H ), 4.42 (m, 1H), 4.63 (m, 1H), 5.35 (s, 2H), 7.46 (t, 1H). mass (542.56) 543.5 351

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3,3- difluoro-1,8-diazaspiro[4,5]decane-8-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 1.82 (m, 4H), 1.92 (m, 2H), 2.39 (m , 2H), 3.04 (d, 1H), 3.44 (m, 3H), 3.59 (m, 3H), 3.66-3.70 (m, 3H), 3.89-4, 00 (m, 1H), 4.02 (m, 1H), 4.16 (d, 1H), 4.44 (m, 1H), 5.42 (m, 2H), 9.27 (s, 1H ). mass (623.68) 624.1 352

(4R,5S,6R)-3-((3S,5S)-5-(1,8-diazaspiro[4,5]decane-8-carbonyl)pyrrolidin-3-ylthio)-6-((R)- 1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.35 (d, 3H), 1.89 (m, 1H), 1.98 (d, 5H), 2.15 (m , 4H), 2.92 (m, 1H), 3.29 (m, 2H), 3.33-3.47 (m, 4H), 3.58 (d, 1H), 3.79 (d, 1H), 4.16 (d, 1H), 4.42 (m, 2H), 4.52 (m, 1H), 4.53 (m, 1H), 5.43 (s, 2H), 9, 28 (s, 1H). mass (587.69) 588.5 353

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( (4aS,7aR)-octahydropyrrolo[3,4-b][1,4]oxazine-6-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2- en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.28 (d, 3H), 1.35 (d, 3H), 1.92 (s, 4H), 2.88-3.11 (m, 1H), 3 .32-3.35(m, 1H), 3.39(m, 2H), 3.57(d, 1H), 3.59-3.76(m, 5H), 3.91-4.00 (m, 2H), 4.16 (d, 1H), 4.40 (m, 1H), 4.57 (m, 1H), 4.87 (m, 1H), 5.43 (s, 2H) , 9.28 (s, 1H). mass (575.64) 576.1 354

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(((R)-thiazolidine-4-carboxamido)methyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.35 (d, 3H), 2.23 (m, 1H), 3.12 (m, 2H), 3.30 (d , 2H), 3.32-3.33(m, 2H), 3.35(m, 2H), 3.59(m, 2H), 3.89(m, 1H), 4.09(m, 1H), 4.13-4.19 (m, 2H), 4.22 (m, 1H), 4.41 (m, 1H), 5.43 (d, 2H), 9.27 (s, 1H ). mass (565.67) 566.0 355

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-tert-butyl-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.36 (d, 3H), 1.46 (s, 9H), 1.92 (m, 1H), 2.08-2 .24 (m, 1H), 2.23-2.50 (m, 2H), 2.89-2.95 (m, 1H), 3.30-3.54 (m, 2H), 3.56 -3.58 (m, 2H), 3.71-3.81 (m, 2H), 3.87-3.94 (m, 2H), 4.06-4.16 (m, 2H), 4 .41-4.43 (m, 2H), 5.47 (d, 2H). masses (589.71)-590 356

(4R,5S,6R)-6-((R)-1-(2-(5-tert-butyl-1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5 -(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.36 (d, 3H), 1.46 (s, 9H) 1.96 (m, 1H), 3.07 (s, 3H), 3.30 (s, 3H), 3.39 (m, 1H), 3.43 (m, 1H), 3.59 (d, 1H), 3.66-3.69 (m, 1H ), 4.02(m, 1H), 4.42(m, 1H), 4.69(m, 1H), 4.71(d, 2H), 5.48-5.51(m, 2H) . masses (548.66) 549. 357

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(2-( 5-(thiophen-2-yl)-1H-tetrazol-1-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.14 (d, 3H), 1.33 (d, 3H), 2.99 (s, 3H), 3.07 (s, 3H), 3.18 (m , 1H), 3.20 (m, 2H), 3.33 (d, 2H), 3.48-3.52 (m, 1H), 3.94 (m, 1H), 4.08 (d, 1H), 4.34-4.38 (m, 1H), 4.58 (m, 1H), 5.58 (s, 2H) 7.35 (s, 1H), 7.74 (s, 1H) , 7.91 (d, 1H). mass (574.68) 574.8 358

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-(2-(5-(thiophen-2-yl)-1H-tetrazol-1-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.36 (d, 3H), 1.73-1.80 (m, 3H), 2.23 (m, 1H), 2 .45-2.49 (m, 1H), 2.83-2.91 (m, 1H), 3.19 (d, 2H), 3.31-3.37 (m, 1H), 3.48 (d, 1H), 3.62 (d, 1H), 3.70 (m, 1H), 3.79 (m, 2H), 4.07 (d, 1H), 4.20-4.27 ( m, 1H), 4.34-4.38 (m, 1H), 5.57 (s, 2H), 7.36 (m, 1H), 7.74 (m, 1H), 7.91 (d , 1H). mass 615.73 615.8 359

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( 4-methylpiperazine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.35 (d, 3H), 2.64 (s, 3H), 2.98 (m, 4H), 3.36 (m , 2H), 3.58 (m, 3H), 3.99 (m, 4H), 4.15 (m, 2H), 4.43 (m, 1H), 4.63 (d, 1H), 4 .81 (d, 1H), 5.43 (m, 2H), 9.37 (s, 1H). mass (547.63) 547.9 360

iodide 4-((2S,4S)-4-((4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-2-carboxy -4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-ylthio)pyrrolidin-2-carbonyl)-1,1-dimethylpiperazin-1-ium ¹ H NMR (D ₂ O) -1.26 (d, 3H), 1.34 (d, 3H), 1.84-1.88 (m, 1H), 2.89-2.96 (m, 1H), 3.20-3.36(m, 7H), 3.50(m, 2H), 3.52(m, 2H), 3.75(m, 5H), 3.96(m, 1H ), 4.15(m, 1H), 4.43-4.56(m, 2H), 4.81(m, 1H), 4.81(m, 1H), 5.47-5.48( m, 2H), 9.28 (s, 1H). mass (iodide 689.57, free base, 562.66) 561.9 361

(4R,5S,6R)-3-((3S,5S)-5-(4-carbamimidoylpiperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2 -(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.15-1.17 (d, 3H), 1.28-1.30 (d, 3H), 2.43 (m, 1H) 2.69 (s, 3H ), 2.70-2.74 (m, 2H), 3.10-3.12 (m, 2H), 3.15-3.16 (m, 1H), 3.37-3.38 (m .2H), 3.61-3.74 (m, 4H), 3.78-3.82 (m, 5H), 4.12-4.17 (m, 2H), 4.45-4.47 (m, 1H), mass 537.2 (M+1)
HPLC 92.1%, C ₂₃ H ₃₆ N ₈ O ₅ S 362

(4R,5S,6S)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)- 1-(methylsulfamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21-1.23 (d, 3H), 1.37-1.39 (d, 3H), 2.26 (m, 1H), 2.48 (m, 1H), 2.94-2.97, (s, 3H), 3.14 (m, 1H), 3.39-3.40 (m, 2H), 3.50-3.51 (m, 2H ), 3.55-3.61 (m, 1H), 3.75-3.89 (m, 2H), 3.90-4.07 (m, 3H), 4.07 (m, 1H), 4.22-4.24 (d, 1H), 4.45-4.46 (m, 1H), HPLC 93.1%; C ₂₀ H ₃₁ N ₅ O ₆ S ₂ , mass 502.4 (M+1). 363

iodide 4-((2S,4S)-4-((4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-2-carboxy -4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-ylthio)pyrrolidine-2-carbonyl)-1-(2-amino-2-oxoethyl)-1- methylpiperazin-1-ia ¹ H NMR (D ₂ O) 1.19-1.20 (d, 3H), 1.33-1.34 (d, 3H), 2.83 (m, 1H), 3.18-3.22 (m, 1H), 3.27 (m, 1H), 3.36 (m, 1H), 3.45 (s, 3H), 3.56 (d, 1H), 3.80 (m, 3H) , 3.89 (m, 3H), 3.99 (m, 3H), 4.12-4.15 (d, 2H), 4.30 (m, 2H), 4.41 (m, 2H), 5.42 (m, 2H), 9.27 (s, 1H); C ₂₅ H ₃₇ IN ₁₀ O ₆ S; HPLC 90.1%; mass 606.2 (M+1) 364

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -aminoethyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) 1.24-1.25 (d, 3H), 1.31-1.32 (d, 3H), 2.55-2.69 (m, 4H), 2.71 -2.73(m, 3H), 2.84-2.86(m, 1H), 3.14-3.17(m, 2H), 3.20-3.24(m, 1H), 3 .39-3.42 (m, 2H), 3.67-3.68 (m, 1H), 3.70-3.71 (m, 4H), 3.89-3.92 (m, 1H) , 4.17-4.20(m, 1H), 4.40-4.80(m, 2H), 5.42(d, 2H), 9.26(s, 1H); C ₂₄ H ₃₆ N ₁₀ O ₅ S; HPLC 91.1%; mass 577.2 365

(4R,5S,6R)-3-((3S,5S)-5-(1,7-diazaspiro[3,5]nonane-7-carbonyl)pyrrolidin-3-ylthio)-6-((R)- 1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.06-1.08 (d, 3H), 1.20-1.22 (d, 3H), 1.62 (m, 1H), 1.99-2, 08 (m, 4H), 2.38-2.43 (m, 2H), 2.78-2.82 (m, 1H), 3.09-3.19 (m, 1H), 3.22- 3.30 (m, 3H), 3.43-3.45 (d, 1H), 3.50-3.60 (m, 2H), 3.79 (m, 2H), 3.90-3, 94 (m, 2H), 4.00-4.02 (m, 1H), 4.29-4.30 (d, 2H), 5.29-5.30 (d, 2H), 9.14 ( s, 1H), wt 574.2 (M+1); C ₂₅ H ₃₅ N ₉ O ₅ S
HPLC 90.4% 366

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(2,7- diazaspiro[3,5]nonane-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.13-1.15 (d, 3H), 1.20-1.22 (d, 3H), 1.69 (m, 1H), 1.95 (m, 4H), 2.60-2.43(m, 2H), 2.72-2.80(m, 1H), 3.09(m, 4H), 3.22-3.24(m, 1H) , 3.44-3.45 (d, 1H), 3.72-3.80 (m, 3H), 3.92-4.03 (m, 3H), 4.17-4.19 (m, 1H), 4.28 (m, 1H), 5.30 (d, 2H), 9.14 (s, 1H), wt 574.2 (M+1); C ₂₅ H ₃₅ N ₉ O ₅ S
HPLC 90% 367

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-carbamimidoylpiperazin- 1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07-1.09 (d, 3H), 1.21-1.23 (d, 3H), 2.76 (m, 1H), 3.21-3, 30 (m, 3H), 3.49-3.50 (m, 5H), 3.63-3.64 (m, 5H), 3.80 (m, 1H), 4.01-4.03 ( m, 1H), 4.28-4.31 (m, 2H), 5.31 (m, 2H), 9.14 (s, 1H), wt 576.4 (M+1); C ₂₃ H ₃₃ N ₁₁ O ₅ S; HPLC 91% 368

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(2,7- diazaspiro[3,5]nonane-7-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17-1.19 (d, 3H), 1.32-1.33 (d, 3H), 1.79 (m, 1H), 1.90 (m, 4H), 2.92 (m, 1H), 3.30-3.34 (m, 2H), 3.48-3.52 (m, 3H), 3.55-3.57 (m, 3H) , 3.97(m, 5H), 4.11-4.13(m, 1H), 4.38-4.42(m, 1H), 4.53(m, 1H), 5.40-5 .41 (m, 2H) 9.26 (s, 1H), wt 574.2 (M+1); C ₂₅ H ₃₅ N ₉ O ₅ S; HPLC 91.5%

Examples 369-378 and 383-451 were prepared by treating the compound of formula (10) with the appropriate R ^A COOH according to the method of Preparations 12, 16 and 17, followed by the method of Example 1.

The cyclization to give carbapenem and the reaction of its enol phosphate with various R ¹ -SH are similar to those described for the preparation of Example 1 (Step 1 and Step 2) or Example 95 (Step 1-3) or Example 298 (Step 2-4) .

Example Structure Analytical data 369

(4R,5S,6R)-6-((R)-1-(3-(1H-тетразол-1-ил)пропанамидо)этил)-3-((3S,5S)-5-((R)-3-аминопирролидин-1-карбонил)пирролидин-3-илтио)-4-метил-7-оксо-1-азабицикло[3,2,0]гепт-2-ен-2-карбоновая кислота

(4R,5S,6R)-6-((R)-1-(3-(1H-tetrazol-1-yl)propanamido)ethyl)-3-((3S,5S)-5-((R)- 3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.11 (d, 3H), 1.23 (d, 3H), 2.04-2.08 (m, 1H), 2.51-2.72 (m, 2H), 2.95 (m, 1H), 3.07-3.19 (m, 2H), 3.34-3.46 (m, 3H), 3.63-3.70 (m, 6H) , 3.73 (m, 1H), 3.78 (m, 2H;, 3.8-4.28 (m, 3H), 9.24 (s, 1H); C23H33N9O5S; HPLC 98.9%; wt 548.3 (M+1) 370

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(4-(pyrimidin-2-ylamino)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.26 (d, 3H), 1.31 (d, 3H), 3.01-3.10 (m, 4H), 3.33-3.35 (m, 3H), 3.78-3.82 (m, 3H), 3.80-3.82 (m, 5H), 4.0-4.1 (m, 4H), 5.4 (m, 2H) , 8.3-8.31 (m, 3H), 9.26 (s, 1H); C27H35N11O5S; HPLC 90.1%; mass 626.20 (M+1) 371

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-amino- 4-(cyanomethyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.29 (d, 3H), 1.76 (m, 2H), 2.80 (m, 2H), 3.01 (m , 1H), 3.34-3.40 (m, 2H), 3.5 (m, 2H), 3.34-3.40 (m, 2H), 3.5 (m, 4H), 3, 86-3.89(m, 2H), 4.0(m, 1H), 4.14-4.16(m, 1H), 4.42(m, 1H), 5.42(m, 2H) , 9.27 (s, 1H); C25H34N10O5S; HPLC 91%; mass 587.2 (M+1) 372

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-cyclopropyl-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -0.98-1.10 (m, 2H) 1.19-1.21 (d, 3H), 1.25-1.27 (m, 2H) 1.32 ( m, 3H), 1.60-2.00 (m, 3H), 2.03-2.04 (m, 2H), 2.09-2.31 (m, 1H), 2.32-2, 60 (m, 1H), 2.70-3.06 (m, 1H), 3.18-3.42 (m, 2H), 3.60-3.63 (m, 1H), 3.70- 3.72 (m, 1H), 3.75-3.78 (m, 2H), 3.88-3.93 (m, 2H), 4.03-4.15 (m, 1H), 4. 41-4.44 (m, 1H), 5.40 (s, 2H); C25H35N9O5S; HPLC 90.1%; mass 574.2 (M+1) 373

¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.34 (d, 3H), 3.00 (s, 3H), 3.02 (m, 1H), 3.06 (s , 3H), 3.07-3.08 (m, 1H), 3.40-3.45 (m, 3H), 3.63-3.75 (m, 1H), 4.02-4.04 (m, 2H), 4.25-4.47 (m, 1H), 4.52-4.68 (m, 1H), 7.69-7.78 (m, 4H), 9.57 (s , 1H); C25H30N8O5S; HPLC 92.2%
Mass 555.1 (M+1) 374

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)benzamido)ethyl)-3-((3S,5S)-5-((R)- 3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.33 (d, 3H), 1.91 (m, 1H), 2.89-2.30 (m, 1H), 3 .25 (m, 1H), 3.31 (m, 1H), 3.42-3.44 (m, 2H), 3.44-3.50 (m, 2H), 3.60-3.69 (m, 1H), 3.73-3.79 (m, 2H), 3.85-3.90 (m, 2H), 4.02-4.04 (m, 2H), 4.36-4 .38 (m, 1H), 4.40 (m, 1H), 7.69 (m, 1H), 7.70-7.81 (m, 3H), 9.57 (s, 1H); C27H33N9O5S; HPLC 96.6%; mass 596.2 (M+1) 375

iodide 4-((2S,4S)-4-((4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-2-carboxy -4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-ylthio)pyrrolidine-2-carbonyl)-1-(2-aminoethyl)-1-methylpiperazine-1- and I ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.89 (m, 2H), 3.29 (m, 2H), 3.31 (s , 3H), 3.36 (m, 2H), 3.56-3.64 (m, 8H), 3.90-3.98 (m, 5H), 4.09 (m, 1H), 4, 40-4.43 (m, 2H), 5.42-5.43 (m, 2H), 9.27 (s, 1H); C25H39IN10O5S; HPLC 91.1%; mass 592.2 free base (M+1) 376

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-(1-sulfamoylazetidine-3 -ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.31 (d, 3H), 3.18-3.21 (m, 1H), 3.52-3.54 (m, 1H), 3.76-3.82(m, 2H), 4.08-4.15(m, 2H), 4.24-4.29(m, 2H), 4.38-4.41( m, 1H), 5.41-5.45 (m, 2H), 9.25 (s, 1H); C16H22N8O6S2; HPLC 90.2%; mass 487.1 (M+1) 377

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(8-azaspiro[ bicyclo[3,2,1]octane-3,3'-pyrrolidine]-8-ylcarbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2 -en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.11 (d, 3H), 1.24 (d, 3H), 1.72 (m, 6H), 1.82 (m, 4H), 2.90-2 .94 (m, 1H), 2.9 (m, 2H), 3.12-3.26 (m, 1H), 3.41-3.45 (m, 3H), 3.45-3.46 (m, 4H), 3.47-3.48 (m, 1H), 4.02-4.05 (m, 1H), 4.26-4.32 (m, 2H), 4.71 (m , 1H), 5.30-5.32 (m, 2H), 9.17 (s, 1H); C28H39N9O5S; HPLC 91.2%; mass 614.4 (M+1) 378

(4R,5S,6R)-6-((R)-1-(2-(5-cyclopropyl-1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-( dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.02-1.05 (m, 2H) 1.20 (d, 3H), 1.25-1.27 (m, 2H), 1.32 (d, 3H ), 1.95-2.02 (m, 3H), 2.99-3.01 (s, 3H), 3.30 (s, 4H), 3.32-3.34 (m, 1H), 3.43-3.48 (m, 1H), 3.58-3.60 (m, 1H), 3.73-3.77 (m, 1H), 4.02-4.05 (m, 1H ), 4.14-4.17 (m, 1H), 4.39-4.43 (m, 1H), 5.38 (s, 2H); C23H32N8O5S; HPLC 96.1%; mass 533.3 (M+1) 379

(4R,5S,6S)-6-((R)-1-((1H-tetrazol-1-yl)methylsulfamido)ethyl)-3-((3S,5S)-5-
(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.27 (d, 3H), 1.77-1.80 (m, 2H), 2.86-2.88 (m, 3H), 2.90-2.97(m, 2H), 3.26-3.31(m, 2H), 3.35-3.37(m, 3H), 3.51-3.56( m, 1H), 3.88-3.92 (m, 1H), 4.11-4.13 (m, 1H), 4.56-4.58 (m, 1H), 6.00-6, 01 (m, 2H), 9.4 (s, 1H); C19H28N8O6S2; HPLC 96.9%; mass 529.5 (M+1) 380

(4R,5S,6S)-6-((R)-1-((1H-tetrazol-1-yl)methylsulfamido)ethyl)-3-((3S,5S)-5-((R)-3- aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.08 (d, 3H), 1.25 (d, 3H), 2.35-2.37 (m, 1H), 2.80-2.90 (m, 1H), 3.16-3.20(m, 2H), 3.28-3.43(m, 3H), 3.48-3.55(m, 1H), 3.56-3.68( m, 3H), 3.74-3.84 (m, 2H), 3.86-4.10 (m, 2H), 4.10-4.13 (m, 1H), 4.13-4, 29 (m, 1H), 6.00 (m, 2H), 9.36 (s, 1H); C21H31N9O6S2; HPLC 92.5%; mass 570.6 (M+1) 381

(4R,5S,6S)-6-((R)-1-((2H-tetrazol-2-yl)methylsulfamido)ethyl)-3-((3S,5S)-5-
(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O)-0.96 (d, 3H), 1.16 (d, 3H), 1.80-1.83 (m, 1H), 2.67 (s, 3H), 2 .85 (s, 3H), 3.05-3.09 (m, 1H), 3.12-3.18 (m, 2H), 3.21-3.33 (m, 2H), 3.71 -3.73(m, 2H), 3.99-4.02(m, 1H), 4.27-4.32(m, 1H), 4.46-4.48(m, 1H), 6 .0 (s, 1H), 8.6 (s, 1H)
C19H28N8O6S2; mass 528.61 (M+1) 382

(4R,5S,6S)-6-((R)-1-((2H-tetrazol-2-yl)methylsulfamido)ethyl)-3-((3S,5S)-5-((R)-3- aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.12 (d, 3H), 1.28 (d, 3H), 2.38-2.42 (m, 2H), 2.82 (m, 1H), 3 .18-3.22 (m, 1H), 3.21-3.41 (m, 3H), 3.51-3.72 (m, 4H), 3.77-3.91 (m, 2H) , 3.03-3.97 (m, 2H), 4.16-4.18 (m, 1H), 4.31 (m, 1H), 6.19-6.24 (m, 2H), 8 .85 (s, 1H)
C21H31N9O6S2; HPLC 93%
Mass 570.3 (M+1) 383

(4R,5S,6R)-6-((R)-1-(2-(5-(dimethylamino)-1H-tetrazol-1-yl)acetamido)ethyl)-3-
((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo
[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.22 (d, 3H), 1.72-1.75 (m, 1H), 2.83 (s, 3H), 2 .95 (s, 9H), 3.19-3.26 (m, 3H), 3.46-3.47 (m, 2H), 3.86 (m, 1H), 4.03-4.05 (m, 1H), 4.30-4.33 (m, 1H), 4.50-4.70 (m, 1H), 5.1 (s, 2H)
C22H33N9O5S; HPLC 94.4%; mass 536.4 (M+1) 384

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-(dimethylamino)-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.22 (d, 3H), 1.8 (m, 1H), 2.03-2.23 (m, 1H), 2 .34-2.36(m, 1H), 2.84(m, 2H), 2.94(m, 6H), 3.17(m, 1H), 3.38-3.39(m, 2H ), 3.46-3.47 (m, 2H), 3.58-3.60 (m, 2H), 3.75-3.78 (m, 2H), 3.94-3.99 (m , 2H), 4.31-4.33 (m, 1H), 5.1 (s, 2H); C24H36N10O5S; HPLC 90%; mass 575.7 (M-1) 385

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-(5-
methoxy-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.12 (d, 3H), 1.22 (d, 3H), 1.80-.185 (m, 1H), 2.91 (s, 3H), 2, 95 (s, 3H), 3.19 (m, 2H), 3.20-3.24 (m, 2H), 3.45-3.46 (m, 1H), 3.55-3.59 ( m, 1H), 3.90 (m, 1H), 4.02 (m, 1H), 4.12 (s, 3H), 4.27-4.30 (m, 1H), 4.99 (s , 2H); C21H30N8O6S; HPLC 96.1%; mass 523.4 (M+1) 386

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-Methoxy-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.11 (d, 3H), 1.22 (d, 3H), 2.14-2.15 (m, 1H), 2.35-2.39 (m, 1H), 2.85-3.00 (m, 1H), 3.20-3.26 (m, 2H), 3.45-3.46 (m, 2H), 3.50-3.56 ( m, 2H), 3.81-3.86 (m, 2H), 3.96-3.97 (m, 2H), 4.02-4.04 (m, 2H), 4.12 (s, 3H), 4.26-4.28(m, 1H), 4.36(m, 1H), 4.94-4.95(m, 2H); C23H33N9O6S; HPLC 90.9%; mass 564.4 (M+1) 387

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(1-((2S,4S)-4-aminopyrrolidine- 2-carbonyl)azetidine-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.32 (m, 3H), 2.49-2.56 (m, 1H), 3.11-3.18 (m, 1H), 3.33(m, 1H), 3.55-3.57(m, 2H), 3.73-3.78(m, 1H), 3.96(m, 2H), 4.02 -4.04 (m, 2H), 4.23 (m, 2H), 4.34-4.49 (m, 2H), 4.75-4.82 (m, 1H), 5.38 (s , 2H), 9.26 (s, 1H); C21H29N9O5S; HPLC 91.1%; mass 520.4 (M+1) 388

(4R,5S,6R)-6-((1R)-1-(2-amino-3,3,3-trifluoropropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 1.94-1.99 (m, 1H), 3.00 (s, 3H), 3 .06 (s, 3H), 3.27 (m, 2H), 3.44-3.48 (m, 2H), 3.71-3.73 (m, 2H), 4.02-4.09 (m, 3H), 4.45 (m, 1H); C20H28F3N5O5S; HPLC 94.9%; mass 508.3 (M+1) 389

(4R,5S,6R)-6-((1R)-1-(2-amino-3,3,3-trifluoropropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.33 (d, 3H), 1.92 (m, 1H), 3.02 (s, 3H), 3.07 (s , 3H), 3.35-3.42 (m, 3H), 3.59-3.61 (m, 3H), 4.02-4.17 (m, 3H), 4.41 (m, 1H ); C20H28F3N5O5S; HPLC 91.7%; mass 508.3 (M+1) 390

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5,6-dihydrotetrazolo[1,5-a]pyrazin-7(8H)-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2- en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.12 (d, 3H), 1.18 (d, 3H), 3.0-3.1 (m, 4H), 3.15-3.20 (m, 5H), 3.30-3.34 (m, 4H), 3.44-3.55 (m, 3H), 3.58-3.61 (m, 4H), 4.29-4.30 ( m, 1H), 4.32-4.41 (m, 3H), 4.42-4.75 (m, 1H); C25H36N10O5S; HPLC 91.5%; mass 589.2 (M+1) 391

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(((R) -3-aminopyrrolidin-1-yl)methyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.27 (d, 3H), 1.92 (m, 3H), 2.66-2.67 (m, 2H), 2 .73-2.79 (m, 2H), 2.84-2.95 (m, 4H), 3.31-3.32 (m, 2H), 3.58-3.59 (m, 2H) , 3.89 (s, 2H), 4.12 (s, 1H), 4.39-4.41 (m, 1H), 5.41 (m, 2H), 9.26 (s, 1H); C22H33N9O4S; HPLC 97.8%; mass 520.4 (M+1) 392

(4R,5S,6R)-6-((R)-1-(2-(5-amino-1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-( dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.32 (d, 3H), 2.08 (m, 1H), 2.97-2.98 (m, 1H), 2 .99 (s, 3H), 3.07-3.08 (m, 1H), 3.11 (s, 3H), 3.30-3.32 (m, 2H), 3.55 (m, 2H ), 3.96 (m, 1H), 4.13-4.15 (m, 1H), 4.40-4.55 (m, 1H), 5.05-5.07 (d, 2H); C20H29N9O5S; HPLC 90.1%; mass 508.3 (M+1) 393

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.91-3.10 (m, 1H), 3.32-3.40 (m, 2H), 3.47-3.52(m, 1H), 3.59-3.63(d, 5H), 3.70-.375(m, 2H), 4.00(m, 1H), 4.14-4.16(m, 2H), 4.40-4.43(m, 1H), 4.56-4.59(m, 2H), 5.42-5.43(d, 2H ), 9.27 (s, 1H); C22H30N8O6S; HPLC 95%; mass 535.3 (M+1) 394

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-(2-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.34 (d, 3H), 1.71-1.90 (m, 1H), 2.32-2.56 (m, 1H), 2.75-2.94 (m, 1H), 3.20-3.23 (d, 2H), 3.36-3.42 (m, 2H), 3.55-3.61 ( m, 2H), 3.64-3.76 (m, 3H), 3.85-3.90 (m, 2H), 4.04-4.08 (m, 2H), 4.13-4, 15 (m, 1H), 4.17-4.29 (m, 1H), 4.39-4.42 (m, 1H); C24H30F3N7O6S; HPLC 90.1%; mass 602.3 (M+1) 395

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -aminoacetyl)piperazin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.94-2.98 (m, 1H), 3.35 (m, 3H), 3 .56-3.71 (m, 10H), 3.97 (m, 1H), 4.07 (m, 2H), 4.13-4.15 (m, 1H), 4.41-4.43 (m, 1H), 4.61-4.79 (m, 1H), 5.42 (m, 2H), 9.27 (s, 1H); C24H34N10O6S; HPLC 91%; mass 591.4 (M+1) 396

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3R,4R )-3,4-dihydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.08-2.14 (m, 1H), 2.99-3.03 (m, 1H), 3.32-3.38 (m, 2H), 3.51-3.69 (m, 4H), 3.75-3.81 (m, 2H), 4.01-4.03 ( m, 1H), 4.14-4.16 (m, 1H), 4.29-4.34 (m, 2H), 4.40-4.43 (m, 1H), 4.58-4, 62 (m, 1H), 5.42-5.43 (m, 2H), 9.27 (s, 1H)
C22H30N8O7S; HPLC 90.1%; mass 551.5 (M+1) 397

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(8-azaspiro[ bicyclo[3,2,1]octane-3,3'-pyrrolidine]-1'-ylcarbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept- 2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.04-2.08 (m, 5H), 2.22-2.23 (m, 6H), 2.91-2.92(m, 1H), 3.28-3.40(m, 4H), 3.49-3.58(m, 2H), 3.63-3.77( m, 2H), 3.94-3.95 (m, 1H), 4.14 (m, 3H), 4.34-4.41 (m, 2H), 5.42 (m, 2H), 9 .27 (s, 1H); C28H39N9O5S; HPLC 94.3%; mass 614.4 (M+1) 398

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-(2-aminoacetamido)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.99-2.13 (m, 1H), 2.19-2.30 (m, 1H), 2.79-3.10 (m, 1H), 3.32-3.34 (d, 2H), 3.46-3.59 (m, 1H), 3.77 (m, 4H) , 3.95(m, 4H), 4.14(m, 1H), 4.15-4.24(m, 1H), 4.46-4.51(m, 3H), 5.42(m , 2H), 9.27 (s, 1H); C24H34N10O6S; HPLC 90.15; mass 591.4 (M+1) 399

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-guanidinopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.28-1.30 (d, 3H), 1.73-1.80 (m, 2H), 1.92 (m, 2H), 3.02-3.08 (m, 2H), 3.34-3.36 (m, 2H), 3.58-3.78 (m, 4H), 4.00 (m, 1H) , 4.13-4.16(m, 1H), 4.41(m, 2H), 4.58(m, 1H), 5.41(m, 2H), 9.27(s, 1H); C23H33N11O5S; HPLC 90.1%; mass 576.3 (M+1) 400

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3R,4S )-3-amino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.34 (d, 3H), 2.97 (m, 1H), 3.36-3.37 (m, 2H), 3 .63-3.65 (m, 2H), 3.95-3.99 (m, 2H), 4.13-4.16 (m, 4H), 4.52-4.54 (m, 2H) , 4.55-4.63 (m, 3H), 5.46 (m, 2H), 9.27 (s, 1H); C22H31N9O6S; HPLC 94.4%
Mass 550.2 (M+1) 401

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-(2-aminoethylamino)pyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.95 (m, 4H), 3.13-3.23 (m, 1H), 3 .30-3.34 (m, 2H), 3.35-3.50 (m, 2H), 3.59-3.63 (m, 2H), 3.72-3.76 (m, 2H) , 3.98 (m, 2H), 4.13-4.16 (m, 4H), 4.40-4.50 (m, 2H), 5.43 (m, 2H), 9.27 (s , 1H); C24H36N10O5S; HPLC 90%; mass 577.4 (M+1) 402

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(pyridin-4-ylcarbamoyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 3.27-3.34 (m, 3H), 3.56-3.65 (m, 3H), 4.11-4.14(m, 2H), 4.39-4.42(m, 2H), 5.42(m, 2H), 7.71-7.72(m, 2H) , 8.49-8.51 (m, 2H) 9.27 (s, 1H); C23H27N9O5S; HPLC 91.56%; mass 542.8 (M+1) 403

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-carboxy-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.36 (d, 3H), 2.28 (m, 1H), 2.49 (m, 1H), 3.05 (m , 1H), 3.38-3.58 (m, 2H), 3.49-3.51 (m, 2H), 3.64-3.67 (m, 2H), 3.74-3.80 (m, 3H), 3.90 (m, 2H), 3.93-4.10 (m, 2H), 4.69 (m, 1H), 5.52 (m, 2H); C23H31N9O7S; HPLC 94.3%; mass 578.3 (M+1) 404

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(aminomethyl )piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.29 (m, 3H), 1.87 (m, 4H), 1.92 (m, 1H), 2.94-2 .95 (m, 1H), 3.23 (m, 3H), 3.30-3.33 (m, 1H), 3.56-3.58 (m, 2H), 3.80 (m, 2H ), 4.10-4.15 (m, 2H), 4.39-4.40 (m, 1H), 4.82 (m, 2H), 4.89 (m, 1H), 5.40- 5.42 (m, 3H), 9.27 (s, 1H); C24H35N9O5S; HPLC 90.1%; mass 562.2 (M+1) 405

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 3-methylazetidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.63 (s, 3H), 2.84 (m, 1H), 3.35 (m , 2H), 3.58 (m, 3H), 3.73 (m, 1H), 3.94 (m, 1H), 4.13-4.16 (m, 2H), 4.32-4, 38 (m, 4H), 5.41-5.42 (d, 2H), 9.27 (s, 1H); C22H31N9O5S; HPLC 90%; mass 533.60 (M+1) 406

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(4-((S)-pyrrolidin-3-yl)piperazin-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.27 (d, 3H), 1.33-1.35 (d, 3H), 2.0-2.05 (m, 1H), 3.21 (m, 1H), 3.31-3.35(m, 1H), 3.47(m, 1H), 3.58-3.61(m, 9H), 3.70-3.78(m, 2H) , 3.79 (m, 2H), 3.90 (m, 4H), 4.11-4.13 (m, 1H), 4.38-4.42 (m, 1H), 5.41-5 .46 (m, 3H), 8.0 (m, 1H), 9.27 (s, 1H); C26H38N10O5S; HPLC 96.4%; mass 603.4 (M+1) 407

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(azetidin-3-ylthio)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.14 (d, 3H), 1.33 (d, 3H), 3.15 (m, 1H), 3.55-3.57 (m, 1H), 4 .0-4.1 (m, 4H), 4.12 (m, 1H), 4.31-4.35 (m, 2H), 4.52-4.59 (m, 2H), 9.27 (s, 1H); C16H21N7O4S; HPLC 99.9%; mass 408.2 (M+1) 408

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(azetidine -3-yl)piperazin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 2.50 (d, 2H), 2.99 (m, 2H), 3.30-3 .32 (m, 1H), 3.43-3.58 (m, 1H), 3.63-3.67 (m, 1H), 3.69-3.72 (m, 6H), 3.90 (m, 4H), 4.10-4.13 (m, 1H), 4.15-4.22 (m, 4H), 4.39-4.43 (m, 1H), 5.41-5 .42 (m, 2H), 9.27-9.31 (d, 1H); C25H36N10O5S; HPLC 97.3%; mass 590.4 (M+1) 409

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( R)-3-aminopyrrolidin-1-yl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 2.86-2.89 (m, 1H), 3.18-3.20 (m, 1H), 3.22-3.27(m, 2H), 3.55-3.59(m, 9H), 3.64-3.69(m, 1H), 3.71-3.85( m, 4H), 4.13-4.35 (m, 1H), 4.35-4.39 (m, 2H), 4.40-4.43 (m, 1H), 4.82 (m, 1H), 5.4-5.42(m, 3H), 7.21-7.33(m, 1H), 7.41-7.43(m, 1H), 9.27(s, 1H) ; C27H40N10O5S; HPLC 90%; mass 617.4 (M+1) 410

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-(dimethylamino)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.24 (d, 3H), 1.33 (m, 3H), 2.31 (m, 1H), 2.56 (m, 1H), 2.90 (s , 6H), 3.10-3.2 (m, 1H), 3.54-3.6 (m, 1H), 3.59 (m, 2H), 3.71-3.76 (m, 2H ), 3.95 (m, 1H), 4.0 (m, 4H), 4.13-4.16 (m, 2H), 4.40-4.43 (m, 1H), 4.50- 4.80 (m, 1H), 5.30-5.42 (m, 2H), 9.25 (s, 1H); C24H35N9O5S; HPLC 94.55%; mass 562.6 (M+1) 411

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2R,4S )-4-amino-2-methylpyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.77 (d, 3H), 1.79 (d, 6H), 2.46 (m, 1H), 2.70-2.74 (m, 1H), 3 .70-3.73(m, 2H), 3.77(m, 2H), 3.88(m, 1H), 4.03-4.05(m, 2H), 4.08(m, 1H ), 4.13-4.15(m, 1H), 4.21-4.23(m, 1H), 4.33(m, 1H), 4.39-4.41(m, 1H), 4.42-4.65(m, 1H), 4.82-4.90(m, 2H), 5.41-5.42(m, 1H), 9.27(s, 1H); C23H33N9O5S; HPLC 93.8%; mass 548.2 (M+1) 412

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4S )-4-amino-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.29 (d, 3H), 2.94 (m, 2H), 3.32 (m, 2H), 3.57-3 .59 (m, 2H), 3.62-3.65 (m, 2H), 3.96 (m, 1H), 4.07-4.10 (m, 3H), 4.13-4.15 (m, 4H), 4.41 (m, 2H), 5.40-5.42 (m, 2H), 9.25-9.27 (s, 1H); C23H33N9O6S
HPLC 92.7%; mass 564.0 (M+1) 413

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3,4- diaminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (3, 3H), 2.96-3.00 (m, 1H), 3.33-3.36 (m, 2H), 3.49 (m, 1H), 3.55-3.58 (m, 1H), 3.61-3.63 (m, 2H), 3.71 (m, 2H), 3.92 -3.97(m, 2H), 4.08(m, 1H), 4.13-4.16(m, 1H), 4.39-4.43(m, 1H), 4.50(m , 1H), 4.82 (m, 1H), 5.42-5.47 (m, 2H), 9.27 (s, 1H); C22H32N10O5S
HPLC 90.6%; mass 549.2 (M+1) 414

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4S )-3-amino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.29 (d, 3H), 1.34 (d, 3H), 1.92 (m, 2H), 3.21-3.31 (m, 1H), 3 .59-3.63 (m, 2H), 3.89-3.92 (m, 4H), 4.00-4.03 (m, 1H), 4.14-4.16 (m, 3H) , 4.40-4.43(m, 1H), 4.61-4.63(m, 2H), 5.41-5.46(m, 2H), 9.27(s, 1H); C22H31N9O6S; HPLC 95%; mass 550.4 (M+1) 415

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(2-aminoethylthio)-4-methyl-7-oxo- 1-azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.14 (d, 3H), 1.28 (d, 3H), 3.01-3.05 (m, 1H), 3.23-3.27 (m, 1H), 3.38-3.40(m, 2H), 3.57-3.59(m, 1H), 3.72(m, 1H), 4.12-4.15(m, 1H) , 4.40-4.43(m, 1H), 4.82(m, 1H), 5.40-5.47(m, 1H), 9.27(s, 1H); C15H21N7O4S; HPLC 90.95; mass 396.3 (M+1) 416

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -hydroxyethyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.92 (m, 1H), 2.55-2.69 (m, 3H) 2, 84-3.01 (m, 4H), 3.32-3.39 (m, 4H), 3.57-3.61 (m, 2H), 3.80-3.83 (m, 2H), 4.00 (m, 2H), 4.13-4.15 (m, 1H), 4.40-4.43 (m, 1H), 4.69-4.71 (m, 1H), 4. 82 (m, 1H), 5.41-5.42 (m, 2H) 9.27 (s, 1H); C24H35N9O6S; HPLC 96.1%; mass 578.2 (M+1) 417

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -amino-2-oxoethyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.86-1.92 (m, 1H), 2.60-2.63 (m, 3H), 3.01-3.18(m, 1H), 3.32-3.36(m, 3H), 3.57-3.62(m, 2H), 3.71-3.99( m, 4H), 4.14-4.16 (m, 1H), 4.40-4.43 (m, 1H), 4.63-4.67 (m, 1H), 4.82 (m, 1H), 5.37-5.42(m, 2H), 7.21-7.23(m, 1H), 7.39-7.43(m, 1H), 9.27(s, 1H) ; C24H34N10O6S; HPLC 96.7%; mass 591.4 (M+1) 418

(4R,5S,6R)-3-((3S,5S)-5-(1,9-diazaspiro[5,5]undecane-9-carbonyl)pyrrolidin-3-ylthio)-6-((R)- 1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.34 (d, 3H), 1.79 (d, 3H), 1.95 (m, 3H), 2.45 (m, 5H), 3.22 (m , 3H), 3.34 (m, 2H), 3.57 (m, 3H), 3.72 (m, 3H), 3.97 (m, 3H), 4.13 (m, 2H), 4 .41 (m, 2H), 5.40-5.42 (m, 2H), 9.27 (s, 1H); C27H39N9O5S; HPLC 93.7%; mass 602.4 (M+1) 419

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(3 -aminopropanoyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.29 (d, 3H), 1.34 (d, 3H), 1.86-1.92 (m, 2H) 2.93 (m, 3H), 3, 28-3.31 (m, 4H), 3.55-3.61 (m, 9H), 4.13-4.15 (m, 1H), 4.59-4.61 (m, 1H), 4.75 (m, 1H), 4.89 (m, 1H), 5.37-5.47 (m, 2H), 9.27 (m, 1H); C25H36N10O6S; HPLC 92.3%; mass 605.3 (M+1) 420

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( S)-2-amino-3-hydroxypropanoyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 3.07-3.21 (m, 1H), 3.36-3.55 (m, 3H), 3.71-3.73(m, 9H), 3.85-3.98(m, 4H), 4.24-4.28(m, 1H), 4.49-4.51( m, 2H), 4.79-4.87 (m, 1H), 5.42 (m, 2H), 9.27 (s, 1H); C25H36N10O7S; HPLC 96.3%; mass 621.2(M+1) 421

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-(2H -1,2,3-triazol-2-yl)azetidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.34 (d, 3H), 2.89 (m, 1H), 3.32-3.36 (m, 2H), 3 .57-3.62 (m, 2H), 3.96 (m, 1H), 4.13-4.16 (d, 1H), 4.42-4.45 (m, 4H), 4.75 -4.82 (m, 3H), 5.3-5.37 (m, 2H), 5.5 (m, 1H), 8.1 (s, 1H), 8.54 (s, 1H), 9.27 (s, 1H); C23H29N11O5S; HPLC 93.5%
Mass 572.2 (M+1) 422

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( 2-aminoacetamido)methyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) 1.29 (d, 3H), 1.34 (d, 3H), 1.82 (m, 4H), 2.47 (m, 1H), 2.79 (m, 1H), 2.94 (m, 1H), 3.2 (m, 2H), 3.34 (m, 1H), 3.57 (m, 4H), 3.76 (m, 4H), 3, 98 (m, 1H), 4.13 (m, 1H), 4.40 (m, 1H), 4.54 (m, 2H), 5.42-5.43 (m, 2H), 9.27 (s, 1H); C26H38N10O6S; HPLC 90%; mass 619.2 (M+1) 423

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(hydroxymethyl )piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 1.83 (m, 6H), 2.84 (m, 1H), 3.0 (m , 1H), 3.32 (m, 1H), 3.48 (m, 1H), 3.57 (m, 2H), 3.70 (m, 1H), 3.78 (m, 3H), 4 .0 (m, 1H), 4.13 (m, 1H), 4.40 (m, 2H), 5.42 (m, 3H), 9.27 (s, 1H); C24H34N8O6S; HPLC 90.2%; mass 563.2 (M+1) 424

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 3-(cyanomethyl)azetidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (3, 3H), 1.85-1.92 (m, 1H), 2.82 (m, 2H), 3 .0 (m, 3H), 3.26 (m, 1H), 3.34 (m, 1H), 3.56 (m, 2H), 3.97 (m, 2H), 4.12-4, 15 (m, 2H), 4.40-4.50 (m, 2H), 5.4 (m, 2H), 9.27 (s, 1H); C23H30N10O5S; HPLC 91.9%; mass 559.2 (M+1) 425

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-amino- 3-fluoropiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.04 (d, 3H), 1.34 (d, 3H) 1.75 (m, 2H), 2.90 (m, 3H), 3.25-3, 34 (m, 5H), 3.56-3.72 (m, 4H), 3.98-3.99 (m, 1H), 4.12-4.14 (m, 1H), 4.40- 4.48 (m, 2H), 5.43 (d, 2H), 9.27 (s, 1H); C23H32FN9O5S; HPLC 92.7%; mass 566.2 (M+1) 426

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(3 -hydroxyazetidin-1-yl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.3 (d, 3H), 1.83-1.85 (m, 2H), 2.82-2.97 (m, 3H), 3.21-3.35(m, 4H), 3.52-3.58(m, 4H), 3.89-3.95(m, 4H), 4.15-4.29( m, 1H), 4.41-4.43 (m, 2H), 4.48-4.51 (m, 1H), 4.58-4.65 (m, 1H), 4.67-4, 68(m, 1H), 4.76-4.83(m, 1H), 5.43(m, 2H), 9.27(s, 1H); C26H37N9O6S; HPLC 96.6%; mass 604.2 (M+1) 427

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4S )-3-guanidino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.82 (m, 2H), 2.85 (m, 1H), 3.35 (m , 1H), 3.63 (m, 3H), 3.74 (m, 3H), 3.89-4.07 (m, 3H), 4.13 (m, 1H), 4.41-4, 45 (m, 2H), 5.42-5.43 (m, 2H), 9.27 (s, 1H); C23H33N11O6S; HPLC 94.1%;
Mass 592.4 (M+1) 428

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( R)-3-aminopyrrolidine-1-carbonyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.30 (d, 3H), 1.45 (m, 2H), 1.92 (m, 4H), 2.38-2 .48 (m, 1H), 2.89-2.93 (m, 3H), 3.28-3.33 (m, 3H), 3.57-3.59 (m, 3H), 3.76 -3.78(m, 4H), 4.0(m, 3H), 4.13(m, 1H), 4.40-4.43(m, 2H), 5.47-5.54(m , 2H), 9.27 (s, 1H); C28H40N10O6S; HPLC 91%; mass 645.6 (M+1) 429

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(3-(piperazin-1-yl)azetidine-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O)-1,20-(d, 3H), 1.34 (d, 3H), 2.7 (m, 3H), 3.24-3.32 (m, 6H), 3.50-3.58(m, 4H), 3.95(m, 1H), 4.13-4.15(m, 2H), 4.18-4.23(m, 4H), 4, 39-4.43 (m, 2H), 5.42-5.47 (m, 3H), 9.27 (s, 1H); C25H36N10O5S; HPLC 90%
Mass 589.3 (M+1) 430

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(4-(piperazine-1-carbonyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.30 (d, 3H), 1.57-1.67 (m, 2H), 1.87-1.90 (m, 3H), 2.9 (m, 2H), 3.1 (m, 1H), 3.26 (m, 5H), 3.5 (m, 4H), 3.83 (m, 2H), 3, 87 (m, 2H), 3.98 (m, 3H), 4.4 (m, 3H), 5.4-5.45 (d, 2H), 9.26 (s, 1H); C28H40N10O6S; mass 644.75 (M+1) 431

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4R )-3-amino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3 H), 1.30 (d, 3H), 2.81 (m, 1H), 3.17 (m, 1H), 3.30- 3.34 (m, 2H), 3.53-3.57 (m, 3H), 3.92-3.93 (m, 2H), 4.12-4.21 (m, 2H), 4. 36-4.40(m, 2H), 4.44-4.55(m, 1H), 4.88(m, 2H), 5.44(m, 2H), 9.24(s, 1H) ; C22H31N9O6S; HPLC 90.6%; mass 550.1 (M+1) 432

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -guanidinoethyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.31 (d, 3H), 1.80-1.82 (m, 1H), 2.55-2.68 (m, 4H), 2.87-2.91(m, 1H), 3.26-3.37(m, 4H), 3.51-3.54(m, 4H), 3.66(m, 2H) , 3.93 (m, 1H), 4.09-4.12 (m, 1H), 4.37-4.40 (m, 1H), 4.49-4.53 (m, 1H), 4 .89 (m, 2H), 5.40 (s, 2H), 9.24 (s, 1H); C25H38N12O5S; HPLC 96.5%; mass 619.2 (M+1) 433

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-amino- 3-fluoropiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.31 (d, 3H), 1.81-1.84 (m, 1H), 2.88-2.90 (m, 2H), 3.27-3.33(m, 4H), 3.42-3.44(m, 1H), 3.48(m, 1H), 3.53-3.54(m, 1H) , 3.69 (m, 2H), 3.92 (m, 1H), 4.09-4.11 (m, 1H), 4.27-4.34 (m, 1H), 4.36-4 .40 (m, 1H), 4.55-4.57 (m, 1H), 4.90 (m, 1H), 5.40 (s, 2H), 9.24 (s, 1H); C23H32FN9O5S; HPLC 93.7%
Mass 566.3 (M+1) 434

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( 2R,4R)-4-aminopyrrolidine-2-carbonyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.30 (d, 3H), 1.90 (m, 2H), 2.66-2.67 (m, 1H), 2 .97-2.98 (m, 1H), 3.11-3.12 (m, 1H), 3.27-3.34 (m, 3H), 3.57-3.58 (m, 2H) , 3.65-3.67 (m, 5H), 3.92-3.95 (m, 2H), 4.09-4.11 (m, 1H), 4.36-4.39 (m, 2H), 4.64-4.65(m, 2H), 4.98(m, 2H), 5.39(s, 2H), 9.23(s, 1H); C27H39N11O6S
HPLC 93%; mass 646.2 (M+1) 435

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(2,8- diazaspiro[4,5]decane-8-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 1.67-1.68 (m, 2H), 1.70-1.71 (m, 2H), 1.82-1.85(m, 1H), 2.94-.297(m, 1H), 3.19-3.20(m, 2H), 3.32-3.35(2H ), 3.37-3.42 (m, 4H), 3.43-3.45 (m, 4H), 3.50-3.53 (m, 1H), 3.54-3.56 (m , 1H), 3.96-3.98 (m, 1H), 4.10-4.11 (m, 1H), 4.37-4.39 (m, 1H), 4.58-4.60 (m, 1H), 5.38-5.40 (m, 2H), 9.24 (s, 1H); C26H37N9O5S; HPLC 90.1%; mass 588.49 (M+1) 436

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(bis(2- hydroxyethyl)carbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.12 (d, 3H), 1.31 (d, 3H), 2.5 (m, 1H), 3.32-3.35 (m, 1H), 3 .42-3.44 (m, 1H), 3.46-3.49 (m, 2H), 3.53-3.56 (m, 2H), 3.57 (m, 2H), 3.59 -3.60 (m, 2H), 3.74-3.95 (m, 1H), 4.11-4.13 (m, 1H), 4.37-4.39 (m, 1H), 4 .41-4.63(m, 1H), 4.80-4.85(m, 1H), 4.85(m, 2H), 5.37-5.40(m, 2H), 9.23 (s, 1H)
C22H32N8O7S; HPLC 90.1%; mass 553.2 (M+1) 437

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( 2-amino-2-oxoethylamino)methyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.17 (d, 3H) 1.31 (d, 3H), 1.86-1.89 (m, 2H), 2.04-2.06 (m, 1H ), 2.82-2.84 (m, 1H), 2.91-2.93 (m, 3H), 3.2-3.24 (m, 1H), 3.29-3.32 (m , 3H), 3.52-3.58 (m, 4H), 3.79-3.80 (m, 3H), 3.95-3.96 (m, 1H), 4.10-4.13 (m, 1H), 4.31-4.38 (m, 2H), 4.57-4.59 (m, 1H), 5.37-5.40 (m, 2H), 9.23 (s , 1H); C26H38N10O6S; HPLC 92.4%; mass 619.4 (M+1) 438

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (d, 3H), 1.97 (m, 1H), 2.12-2.17 (m, 3H), 2 .64 (m, 3H), 3.00-3.07 (m, 3H), 3.27-3.31 (m, 2H), 3.42-3.43 (m, 2H), 3.65 -3.70(m, 3H), 4.01(m, 1H), 4.11-4.13(m, 1H), 4.28-4.30(m, 1H), 4.37-4 .40 (m, 1H), 4.53-4.57 (m, 1H), 5.40 (d, 2H), 9.25 (s, 1H); C25H35N9O5S; HPLC 92.6%; mass 574.4 (M+1) 439

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.30-1.32 (d, 3H), 1.75-1.77 (m, 2H), 2.11-2, 16 (m, 3H), 3.22-3.23 (m, 3H), 3.30-3.36 (m, 2H), 3.40-3.44 (m, 3H), 3.53- 3.55 (m, 2H), 3.79-3.89 (m, 3H), 4.09-4.10 (m, 1H), 4.22-4.27 (m, 1H), 4. 37-4.40 (m, 2H), 5.40 (m, 2H), 9.24 (s, 1H); C25H35N9O5S; HPLC 97.4%; mass 574.2 (M+1) 440

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4R )-4-amino-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.16-1.18 (d, 3H), 1.31-1.32 (d, 3H), 2.24-2.28 (m, 1H), 2, 42-2.49(m, 1H), 2.98(m, 1H), 3.38(m, 2H), 3.62-3.65(m, 4H), 3.76-3.77( m, 2H), 3.87-3.89 (m, 2H), 3.92 (m, 1H), 4.11-4.17 (m, 2H), 4.37-4.40 (m, 2H), 5.39 (s, 2H), 9.24 (s, 1H); C23H33N9O6S; HPLC 94.6%; mass 564.3 (M+1) 441

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4S )-4-amino-2-(methylsulfamido-methyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.17-1.19 (d, 3H), 1.31-1.33 (d, 3H), 1.99-2.02 (m, 2H), 2, 62-2.68 (m, 1H), 2.92-2.97 (m, 2H), 3.09-3.33 (m, 4H), 3.52-3.62 (m, 3H), 3.92 (m, 2H), 4.11-4.13 (m, 2H), 4.28 (m, 1H), 4.37-4.41 (m, 3H), 4.98 (m, 1H), 5.40 (s, 2H), 9.25 (s, 1H); C24H36N10O7S2; HPLC 91.2%; mass 641.2 (M+1) 442

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( S)-3-amino-2-hydroxypropyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.28 (d, 3H), 1.33 (d, 3H), 2.55-2.58 (m, 6H), 2.60-2.63 (m, 2H), 2.93-2.96 (m, 3H), 3.14-3.15 (m, 1H), 3.15-3.18 (m, 3H), 3.51-3.55 ( m, 2H), 3.56-3.58 (m, 2H), 3.95 (m, 1H), 4.12-4.15 (m, 1H), 4.39-4.42 (m, 1H), 4.7 (m, 1H), 5.40-5.42 (m, 2H), 9.26 (s, 1H); C25H38N10O6S; HPLC 96.9%; mass 607.20 (M+1) 443

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( 2-aminoethylamino)methyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (m, 3H), 1.33 (d, 3H), 1.93 (m, 1H), 2.3 (m, 2H), 2.79 (m , 2H), 2.81 (m, 2H), 2.96 (m, 3H), 3.10 (m, 1H), 3.21-3.22 (m, 2H), 3.58-3, 61 (m, 3H), 3.81-3.84 (m, 3H), 4.0 (m, 1H), 4.2 (m, 1H), 4.26-4.28 (m, 2H) , 4.40-4.42(m, 2H), 5.39-5.43(m, 2H), 9.27(s, 1H); C26H40N10O5S; HPLC 90.2%
Mass 605.2 (M+1) 444

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4R )-4-amino-2-(aminomethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 2.23 (m, 1H), 2.40-2.43 (m, 1H), 2 .86 (m, 1H), 3.19-3.27 (m, 4H), 3.50-3.56 (m, 2H), 3.76 (m, 1H), 3.95 (m, 2H ), 4.07-4.13 (m, 2H), 4.35-4.42 (m, 2H), 4.55 (m, 1H), 5.40-5.44 (m, 2H), 9.2 (s, 1H); C23H34N10O5S; HPLC 90.0%; mass 563.4 (M+1) 445

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(3 -aminopropyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (d, 3H), 1.90 (m, 1H), 2.59 (m, 4H), 2.60 (m , 2H), 3.01-3.05 (m, 4H), 3.36-.3.38 (m, 2H), 3.56-3.57 (m, 5H), 3.71 (m, 3H), 4.01-4.05(m, 1H), 4.11-4.13(m, 1H), 4.39(m, 1H), 5.39-5.40(m, 2H) , 9.25 (s, 1H); C25H38N10O5S; HPLC 96.4%; mass 591.4 (M+1) 446

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -guanidinoacetyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.31 (d, 3H), 1.78-1.84 (m, 1H), 2.94-2.95 (m, 1H), 3.28-3.34(m, 2H), 3.53-3.58(m, 5H), 3.62-3.68(m, 4H), 3.95(m, 1H) , 4.09-4.11(m, 2H), 4.23(m, 2H), 4.30-4.38(m, 1H), 4.58(m, 1H), 5.39-5 .43 (m, 2H), 9.24 (s, 1H); C25H36N12O6S
HPLC 93.6%; mass 633.6 (M+1) 447

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4R )-4-amino-2-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3,2, 0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.08 (d, 3H), 1.21 (d, 3H), 2.25 (m, 2H), 2.35-2.44 (m, 2H), 2 .87 (m, 1H), 3.14 (m, 1H), 3.22-3.26 (m, 2H), 3.29-3.30 (m, 2H), 3.43-3.46 (m, 1H), 3.50-3.59 (m, 2H), 3.78 (m, 1H), 3.80-3.86 (m, 3H), 3.93-3.95 (m , 1H), 4.00-4.02 (m, 2H), 4.27-4.29 (m, 2H), 4.82-4.86 (m, 1H), 5.32-5.34 (m, 2H), 9.14 (s, 1H); C27H39N11O6S
HPLC 93.0%; mass 646.4 (M+1) 448

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2H -1,2,3-triazol-2-yl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.17-1.19 (d, 3H), 1.31-1.33 (d, 3H), 2.00-2.07 (m, 2H), 2, 28-2.31(m, 2H), 3.11-3.14(m, 2H), 3.31(m, 1H), 3.45-3.48(m, 2H), 3.55- 3.58 (m, 1H), 3.70-3.80 (m, 1H), 3.85-3.95 (m, 1H), 4.05 (m, 1H), 4.12-4, 14 (m, 1H), 4.38-4.42 (m, 2H), 4.79-4.91 (m, 3H), 5.39-5.40 (s, 2H), 7.78 ( s, 2H), 9.24 (s, 1H); C25H33N11O5S; HPLC 97.4%; mass 600.4 (M+1) 449

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((S)-1-(2-aminoacetyl)pyrrolidine- 3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.27 (d, 3H), 2.3-2.5 (m, 1H), 3.32-3.41 (m, 3H), 3.56-3.60(m, 2H), 3.63-3.88(m, 2H), 3.90-3.96(m, 3H), 4.11-4.15( m, 1H), 4.38-4.42 (m, 1H), 5.40-5.41 (d, 2H), 9.25 (s, 1H); C19H26N8O5S; HPLC 95.3%; mass 479.3 (M+1) 450

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( R)-3-amino-2-hydroxypropyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (m, 3H), 1.89 (m, 2H), 2.54-2.59 (m, 4H), 2 .60-2.62 (m, 2H), 2.90-2.92 (d, 2H), 3.13-3.14 (m, 1H), 3.3 (m, 2H), 3.54 -3.57 (m, 4H), 3.59 (m, 1H), 4.1-4.13 (m, 1H), 4.14 (m, 2H), 4.39 (m, 1H), 4.7 (m, 1H), 5.39-5.40 (m, 2H), 9.25 (s, 1H); C25H38N10O6S; HPLC 90.1%; mass 607.2 (M+1) 451

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(4-(2-(piperazin-1-yl)ethyl)piperazin-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.92 (m, 1H), 2.68-2.76 (m, 6H), 2 .82 (m, 4H), 3.01 (m, 3H), 3.28-3.33 (m, 6H), 3.57-3.59 (m, 6H), 4.00-4.16 (m, 2H), 4.39-4.43 (m, 2H), 5.41-5.42 (m, 2H), 9.27 (s, 1H); C28H43N11O5S; HPLC 92.9%; mass 646.6 (M+1) Example Structure Analytical data 369

(4R,5S,6R)-6-((R)-1-(3-(1H-tetrazol-1-yl)propanamido)ethyl)-3-((3S,5S)-5-((R)- 3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.11 (d, 3H), 1.23 (d, 3H), 2.04-2.08 (m, 1H), 2.51-2.72 (m, 2H), 2.95 (m, 1H), 3.07-3.19 (m, 2H), 3.34-3.46 (m, 3H), 3.63-3.70 (m, 6H) , 3.73 (m, 1H), 3.78 (m, 2H;, 3.8-4.28 (m, 3H), 9.24 (s, 1H); C23H33N9O5S; HPLC 98.9%; wt 548.3 (M+1) 370

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(4-(pyrimidin-2-ylamino)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.26 (d, 3H), 1.31 (d, 3H), 3.01-3.10 (m, 4H), 3.33-3.35 (m, 3H), 3.78-3.82 (m, 3H), 3.80-3.82 (m, 5H), 4.0-4.1 (m, 4H), 5.4 (m, 2H) , 8.3-8.31 (m, 3H), 9.26 (s, 1H); C27H35N11O5S; HPLC 90.1%; mass 626.20 (M+1) 371

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-amino- 4-(cyanomethyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.29 (d, 3H), 1.76 (m, 2H), 2.80 (m, 2H), 3.01 (m , 1H), 3.34-3.40 (m, 2H), 3.5 (m, 2H), 3.34-3.40 (m, 2H), 3.5 (m, 4H), 3, 86-3.89(m, 2H), 4.0(m, 1H), 4.14-4.16(m, 1H), 4.42(m, 1H), 5.42(m, 2H) , 9.27 (s, 1H); C25H34N10O5S; HPLC 91%; mass 587.2 (M+1) 372

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-cyclopropyl-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -0.98-1.10 (m, 2H) 1.19-1.21 (d, 3H), 1.25-1.27 (m, 2H) 1.32 ( m, 3H), 1.60-2.00 (m, 3H), 2.03-2.04 (m, 2H), 2.09-2.31 (m, 1H), 2.32-2, 60 (m, 1H), 2.70-3.06 (m, 1H), 3.18-3.42 (m, 2H), 3.60-3.63 (m, 1H), 3.70- 3.72 (m, 1H), 3.75-3.78 (m, 2H), 3.88-3.93 (m, 2H), 4.03-4.15 (m, 1H), 4. 41-4.44 (m, 1H), 5.40 (s, 2H); C25H35N9O5S; HPLC 90.1%; mass 574.2 (M+1) 373

¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.34 (d, 3H), 3.00 (s, 3H), 3.02 (m, 1H), 3.06 (s , 3H), 3.07-3.08 (m, 1H), 3.40-3.45 (m, 3H), 3.63-3.75 (m, 1H), 4.02-4.04 (m, 2H), 4.25-4.47 (m, 1H), 4.52-4.68 (m, 1H), 7.69-7.78 (m, 4H), 9.57 (s , 1H); C25H30N8O5S; HPLC 92.2%
Mass 555.1 (M+1) 374

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)benzamido)ethyl)-3-((3S,5S)-5-((R)- 3-Aminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.33 (d, 3H), 1.91 (m, 1H), 2.89-2.30 (m, 1H), 3 .25 (m, 1H), 3.31 (m, 1H), 3.42-3.44 (m, 2H), 3.44-3.50 (m, 2H), 3.60-3.69 (m, 1H), 3.73-3.79 (m, 2H), 3.85-3.90 (m, 2H), 4.02-4.04 (m, 2H), 4.36-4 .38 (m, 1H), 4.40 (m, 1H), 7.69 (m, 1H), 7.70-7.81 (m, 3H), 9.57 (s, 1H); C27H33N9O5S; HPLC 96.6%; mass 596.2 (M+1) 375

iodide 4-((2S,4S)-4-((4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-2-carboxy -4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-ylthio)pyrrolidine-2-carbonyl)-1-(2-aminoethyl)-1-methylpiperazine-1- and I ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.89 (m, 2H), 3.29 (m, 2H), 3.31 (s , 3H), 3.36 (m, 2H), 3.56-3.64 (m, 8H), 3.90-3.98 (m, 5H), 4.09 (m, 1H), 4, 40-4.43 (m, 2H), 5.42-5.43 (m, 2H), 9.27 (s, 1H); C25H39IN10O5S; HPLC 91.1%; mass 592.2 free base (M+1) 376

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-(1-sulfamoylazetidine-3 -ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.31 (d, 3H), 3.18-3.21 (m, 1H), 3.52-3.54 (m, 1H), 3.76-3.82(m, 2H), 4.08-4.15(m, 2H), 4.24-4.29(m, 2H), 4.38-4.41( m, 1H), 5.41-5.45 (m, 2H), 9.25 (s, 1H); C16H22N8O6S2; HPLC 90.2%; mass 487.1 (M+1) 377

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(8-azaspiro[ bicyclo[3,2,1]octane-3,3'-pyrrolidine]-8-ylcarbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2 -en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.11 (d, 3H), 1.24 (d, 3H), 1.72 (m, 6H), 1.82 (m, 4H), 2.90-2 .94 (m, 1H), 2.9 (m, 2H), 3.12-3.26 (m, 1H), 3.41-3.45 (m, 3H), 3.45-3.46 (m, 4H), 3.47-3.48 (m, 1H), 4.02-4.05 (m, 1H), 4.26-4.32 (m, 2H), 4.71 (m , 1H), 5.30-5.32 (m, 2H), 9.17 (s, 1H); C28H39N9O5S; HPLC 91.2%; mass 614.4 (M+1) 378

(4R,5S,6R)-6-((R)-1-(2-(5-cyclopropyl-1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-( dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.02-1.05 (m, 2H) 1.20 (d, 3H), 1.25-1.27 (m, 2H), 1.32 (d, 3H ), 1.95-2.02 (m, 3H), 2.99-3.01 (s, 3H), 3.30 (s, 4H), 3.32-3.34 (m, 1H), 3.43-3.48 (m, 1H), 3.58-3.60 (m, 1H), 3.73-3.77 (m, 1H), 4.02-4.05 (m, 1H ), 4.14-4.17 (m, 1H), 4.39-4.43 (m, 1H), 5.38 (s, 2H); C23H32N8O5S; HPLC 96.1%; mass 533.3 (M+1) 379

(4R,5S,6S)-6-((R)-1-((1H-tetrazol-1-yl)methylsulfamido)ethyl)-3-((3S,5S)-5-
(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.27 (d, 3H), 1.77-1.80 (m, 2H), 2.86-2.88 (m, 3H), 2.90-2.97(m, 2H), 3.26-3.31(m, 2H), 3.35-3.37(m, 3H), 3.51-3.56( m, 1H), 3.88-3.92 (m, 1H), 4.11-4.13 (m, 1H), 4.56-4.58 (m, 1H), 6.00-6, 01 (m, 2H), 9.4 (s, 1H); C19H28N8O6S2; HPLC 96.9%; mass 529.5 (M+1) 380

(4R,5S,6S)-6-((R)-1-((1H-tetrazol-1-yl)methylsulfamido)ethyl)-3-((3S,5S)-5-((R)-3- aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.08 (d, 3H), 1.25 (d, 3H), 2.35-2.37 (m, 1H), 2.80-2.90 (m, 1H), 3.16-3.20(m, 2H), 3.28-3.43(m, 3H), 3.48-3.55(m, 1H), 3.56-3.68( m, 3H), 3.74-3.84 (m, 2H), 3.86-4.10 (m, 2H), 4.10-4.13 (m, 1H), 4.13-4, 29 (m, 1H), 6.00 (m, 2H), 9.36 (s, 1H); C21H31N9O6S2; HPLC 92.5%; mass 570.6 (M+1) 381

(4R,5S,6S)-6-((R)-1-((2H-tetrazol-2-yl)methylsulfamido)ethyl)-3-((3S,5S)-5-
(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O)-0.96 (d, 3H), 1.16 (d, 3H), 1.80-1.83 (m, 1H), 2.67 (s, 3H), 2 .85 (s, 3H), 3.05-3.09 (m, 1H), 3.12-3.18 (m, 2H), 3.21-3.33 (m, 2H), 3.71 -3.73(m, 2H), 3.99-4.02(m, 1H), 4.27-4.32(m, 1H), 4.46-4.48(m, 1H), 6 .0 (s, 1H), 8.6 (s, 1H)
C19H28N8O6S2; mass 528.61 (M+1) 382

(4R,5S,6S)-6-((R)-1-((2H-tetrazol-2-yl)methylsulfamido)ethyl)-3-((3S,5S)-5-((R)-3- aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.12 (d, 3H), 1.28 (d, 3H), 2.38-2.42 (m, 2H), 2.82 (m, 1H), 3 .18-3.22 (m, 1H), 3.21-3.41 (m, 3H), 3.51-3.72 (m, 4H), 3.77-3.91 (m, 2H) , 3.03-3.97 (m, 2H), 4.16-4.18 (m, 1H), 4.31 (m, 1H), 6.19-6.24 (m, 2H), 8 .85 (s, 1H)
C21H31N9O6S2; HPLC 93%
Mass 570.3 (M+1) 383

(4R,5S,6R)-6-((R)-1-(2-(5-(dimethylamino)-1H-tetrazol-1-yl)acetamido)ethyl)-3-
((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo
[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.22 (d, 3H), 1.72-1.75 (m, 1H), 2.83 (s, 3H), 2 .95 (s, 9H), 3.19-3.26 (m, 3H), 3.46-3.47 (m, 2H), 3.86 (m, 1H), 4.03-4.05 (m, 1H), 4.30-4.33 (m, 1H), 4.50-4.70 (m, 1H), 5.1 (s, 2H)
C22H33N9O5S; HPLC 94.4%; mass 536.4 (M+1) 384

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-(dimethylamino)-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.22 (d, 3H), 1.8 (m, 1H), 2.03-2.23 (m, 1H), 2 .34-2.36(m, 1H), 2.84(m, 2H), 2.94(m, 6H), 3.17(m, 1H), 3.38-3.39(m, 2H ), 3.46-3.47 (m, 2H), 3.58-3.60 (m, 2H), 3.75-3.78 (m, 2H), 3.94-3.99 (m , 2H), 4.31-4.33 (m, 1H), 5.1 (s, 2H); C24H36N10O5S; HPLC 90%; mass 575.7 (M-1) 385

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-(5-
methoxy-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.12 (d, 3H), 1.22 (d, 3H), 1.80-.185 (m, 1H), 2.91 (s, 3H), 2, 95 (s, 3H), 3.19 (m, 2H), 3.20-3.24 (m, 2H), 3.45-3.46 (m, 1H), 3.55-3.59 ( m, 1H), 3.90 (m, 1H), 4.02 (m, 1H), 4.12 (s, 3H), 4.27-4.30 (m, 1H), 4.99 (s , 2H); C21H30N8O6S; HPLC 96.1%; mass 523.4 (M+1) 386

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-Methoxy-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.11 (d, 3H), 1.22 (d, 3H), 2.14-2.15 (m, 1H), 2.35-2.39 (m, 1H), 2.85-3.00 (m, 1H), 3.20-3.26 (m, 2H), 3.45-3.46 (m, 2H), 3.50-3.56 ( m, 2H), 3.81-3.86 (m, 2H), 3.96-3.97 (m, 2H), 4.02-4.04 (m, 2H), 4.12 (s, 3H), 4.26-4.28(m, 1H), 4.36(m, 1H), 4.94-4.95(m, 2H); C23H33N9O6S; HPLC 90.9%; mass 564.4 (M+1) 387

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(1-((2S,4S)-4-aminopyrrolidine- 2-carbonyl)azetidine-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.32 (m, 3H), 2.49-2.56 (m, 1H), 3.11-3.18 (m, 1H), 3.33(m, 1H), 3.55-3.57(m, 2H), 3.73-3.78(m, 1H), 3.96(m, 2H), 4.02 -4.04 (m, 2H), 4.23 (m, 2H), 4.34-4.49 (m, 2H), 4.75-4.82 (m, 1H), 5.38 (s , 2H), 9.26 (s, 1H); C21H29N9O5S; HPLC 91.1%; mass 520.4 (M+1) 388

(4R,5S,6R)-6-((1R)-1-(2-amino-3,3,3-trifluoropropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 1.94-1.99 (m, 1H), 3.00 (s, 3H), 3 .06 (s, 3H), 3.27 (m, 2H), 3.44-3.48 (m, 2H), 3.71-3.73 (m, 2H), 4.02-4.09 (m, 3H), 4.45 (m, 1H); C20H28F3N5O5S; HPLC 94.9%; mass 508.3 (M+1) 389

(4R,5S,6R)-6-((1R)-1-(2-amino-3,3,3-trifluoropropanamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidine-3 -ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.33 (d, 3H), 1.92 (m, 1H), 3.02 (s, 3H), 3.07 (s , 3H), 3.35-3.42 (m, 3H), 3.59-3.61 (m, 3H), 4.02-4.17 (m, 3H), 4.41 (m, 1H ); C20H28F3N5O5S; HPLC 91.7%; mass 508.3 (M+1) 390

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5,6-dihydrotetrazolo[1,5-a]pyrazin-7(8H)-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2- en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.12 (d, 3H), 1.18 (d, 3H), 3.0-3.1 (m, 4H), 3.15-3.20 (m, 5H), 3.30-3.34 (m, 4H), 3.44-3.55 (m, 3H), 3.58-3.61 (m, 4H), 4.29-4.30 ( m, 1H), 4.32-4.41 (m, 3H), 4.42-4.75 (m, 1H); C25H36N10O5S; HPLC 91.5%; mass 589.2 (M+1) 391

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(((R) -3-aminopyrrolidin-1-yl)methyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.27 (d, 3H), 1.92 (m, 3H), 2.66-2.67 (m, 2H), 2 .73-2.79 (m, 2H), 2.84-2.95 (m, 4H), 3.31-3.32 (m, 2H), 3.58-3.59 (m, 2H) , 3.89 (s, 2H), 4.12 (s, 1H), 4.39-4.41 (m, 1H), 5.41 (m, 2H), 9.26 (s, 1H); C22H33N9O4S; HPLC 97.8%; mass 520.4 (M+1) 392

(4R,5S,6R)-6-((R)-1-(2-(5-amino-1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-( dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.32 (d, 3H), 2.08 (m, 1H), 2.97-2.98 (m, 1H), 2 .99 (s, 3H), 3.07-3.08 (m, 1H), 3.11 (s, 3H), 3.30-3.32 (m, 2H), 3.55 (m, 2H ), 3.96 (m, 1H), 4.13-4.15 (m, 1H), 4.40-4.55 (m, 1H), 5.05-5.07 (d, 2H); C20H29N9O5S; HPLC 90.1%; mass 508.3 (M+1) 393

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.91-3.10 (m, 1H), 3.32-3.40 (m, 2H), 3.47-3.52(m, 1H), 3.59-3.63(d, 5H), 3.70-.375(m, 2H), 4.00(m, 1H), 4.14-4.16(m, 2H), 4.40-4.43(m, 1H), 4.56-4.59(m, 2H), 5.42-5.43(d, 2H ), 9.27 (s, 1H); C22H30N8O6S; HPLC 95%; mass 535.3 (M+1) 394

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-(2-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.34 (d, 3H), 1.71-1.90 (m, 1H), 2.32-2.56 (m, 1H), 2.75-2.94 (m, 1H), 3.20-3.23 (d, 2H), 3.36-3.42 (m, 2H), 3.55-3.61 ( m, 2H), 3.64-3.76 (m, 3H), 3.85-3.90 (m, 2H), 4.04-4.08 (m, 2H), 4.13-4, 15 (m, 1H), 4.17-4.29 (m, 1H), 4.39-4.42 (m, 1H); C24H30F3N7O6S; HPLC 90.1%; mass 602.3 (M+1) 395

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -aminoacetyl)piperazin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.94-2.98 (m, 1H), 3.35 (m, 3H), 3 .56-3.71 (m, 10H), 3.97 (m, 1H), 4.07 (m, 2H), 4.13-4.15 (m, 1H), 4.41-4.43 (m, 1H), 4.61-4.79 (m, 1H), 5.42 (m, 2H), 9.27 (s, 1H); C24H34N10O6S; HPLC 91%; mass 591.4 (M+1) 396

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3R,4R )-3,4-dihydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.08-2.14 (m, 1H), 2.99-3.03 (m, 1H), 3.32-3.38 (m, 2H), 3.51-3.69 (m, 4H), 3.75-3.81 (m, 2H), 4.01-4.03 ( m, 1H), 4.14-4.16 (m, 1H), 4.29-4.34 (m, 2H), 4.40-4.43 (m, 1H), 4.58-4, 62 (m, 1H), 5.42-5.43 (m, 2H), 9.27 (s, 1H)
C22H30N8O7S; HPLC 90.1%; mass 551.5 (M+1) 397

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(8-azaspiro[ bicyclo[3,2,1]octane-3,3'-pyrrolidine]-1'-ylcarbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept- 2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.04-2.08 (m, 5H), 2.22-2.23 (m, 6H), 2.91-2.92(m, 1H), 3.28-3.40(m, 4H), 3.49-3.58(m, 2H), 3.63-3.77( m, 2H), 3.94-3.95 (m, 1H), 4.14 (m, 3H), 4.34-4.41 (m, 2H), 5.42 (m, 2H), 9 .27 (s, 1H); C28H39N9O5S; HPLC 94.3%; mass 614.4 (M+1) 398

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-(2-aminoacetamido)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.99-2.13 (m, 1H), 2.19-2.30 (m, 1H), 2.79-3.10 (m, 1H), 3.32-3.34 (d, 2H), 3.46-3.59 (m, 1H), 3.77 (m, 4H) , 3.95(m, 4H), 4.14(m, 1H), 4.15-4.24(m, 1H), 4.46-4.51(m, 3H), 5.42(m , 2H), 9.27 (s, 1H); C24H34N10O6S; HPLC 90.15; mass 591.4 (M+1) 399

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-guanidinopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.28-1.30 (d, 3H), 1.73-1.80 (m, 2H), 1.92 (m, 2H), 3.02-3.08 (m, 2H), 3.34-3.36 (m, 2H), 3.58-3.78 (m, 4H), 4.00 (m, 1H) , 4.13-4.16(m, 1H), 4.41(m, 2H), 4.58(m, 1H), 5.41(m, 2H), 9.27(s, 1H); C23H33N11O5S; HPLC 90.1%; mass 576.3 (M+1) 400

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3R,4S )-3-amino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.34 (d, 3H), 2.97 (m, 1H), 3.36-3.37 (m, 2H), 3 .63-3.65 (m, 2H), 3.95-3.99 (m, 2H), 4.13-4.16 (m, 4H), 4.52-4.54 (m, 2H) , 4.55-4.63 (m, 3H), 5.46 (m, 2H), 9.27 (s, 1H); C22H31N9O6S; HPLC 94.4%
Mass 550.2 (M+1) 401

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-(2-aminoethylamino)pyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.95 (m, 4H), 3.13-3.23 (m, 1H), 3 .30-3.34 (m, 2H), 3.35-3.50 (m, 2H), 3.59-3.63 (m, 2H), 3.72-3.76 (m, 2H) , 3.98 (m, 2H), 4.13-4.16 (m, 4H), 4.40-4.50 (m, 2H), 5.43 (m, 2H), 9.27 (s , 1H); C24H36N10O5S; HPLC 90%; mass 577.4 (M+1) 402

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(pyridin-4-ylcarbamoyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 3.27-3.34 (m, 3H), 3.56-3.65 (m, 3H), 4.11-4.14(m, 2H), 4.39-4.42(m, 2H), 5.42(m, 2H), 7.71-7.72(m, 2H) , 8.49-8.51 (m, 2H) 9.27 (s, 1H); C23H27N9O5S; HPLC 91.56%; mass 542.8 (M+1) 403

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(5-carboxy-1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.36 (d, 3H), 2.28 (m, 1H), 2.49 (m, 1H), 3.05 (m , 1H), 3.38-3.58 (m, 2H), 3.49-3.51 (m, 2H), 3.64-3.67 (m, 2H), 3.74-3.80 (m, 3H), 3.90 (m, 2H), 3.93-4.10 (m, 2H), 4.69 (m, 1H), 5.52 (m, 2H); C23H31N9O7S; HPLC 94.3%; mass 578.3 (M+1) 404

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(aminomethyl )piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.29 (m, 3H), 1.87 (m, 4H), 1.92 (m, 1H), 2.94-2 .95 (m, 1H), 3.23 (m, 3H), 3.30-3.33 (m, 1H), 3.56-3.58 (m, 2H), 3.80 (m, 2H ), 4.10-4.15 (m, 2H), 4.39-4.40 (m, 1H), 4.82 (m, 2H), 4.89 (m, 1H), 5.40- 5.42 (m, 3H), 9.27 (s, 1H); C24H35N9O5S; HPLC 90.1%; mass 562.2 (M+1) 405

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 3-methylazetidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.63 (s, 3H), 2.84 (m, 1H), 3.35 (m , 2H), 3.58 (m, 3H), 3.73 (m, 1H), 3.94 (m, 1H), 4.13-4.16 (m, 2H), 4.32-4, 38 (m, 4H), 5.41-5.42 (d, 2H), 9.27 (s, 1H); C22H31N9O5S; HPLC 90%; mass 533.60 (M+1) 406

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(4-((S)-pyrrolidin-3-yl)piperazin-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.27 (d, 3H), 1.33-1.35 (d, 3H), 2.0-2.05 (m, 1H), 3.21 (m, 1H), 3.31-3.35(m, 1H), 3.47(m, 1H), 3.58-3.61(m, 9H), 3.70-3.78(m, 2H) , 3.79 (m, 2H), 3.90 (m, 4H), 4.11-4.13 (m, 1H), 4.38-4.42 (m, 1H), 5.41-5 .46 (m, 3H), 8.0 (m, 1H), 9.27 (s, 1H); C26H38N10O5S; HPLC 96.4%; mass 603.4 (M+1) 407

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(azetidin-3-ylthio)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.14 (d, 3H), 1.33 (d, 3H), 3.15 (m, 1H), 3.55-3.57 (m, 1H), 4 .0-4.1 (m, 4H), 4.12 (m, 1H), 4.31-4.35 (m, 2H), 4.52-4.59 (m, 2H), 9.27 (s, 1H); C16H21N7O4S; HPLC 99.9%; mass 408.2 (M+1) 408

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(azetidine -3-yl)piperazin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 2.50 (d, 2H), 2.99 (m, 2H), 3.30-3 .32 (m, 1H), 3.43-3.58 (m, 1H), 3.63-3.67 (m, 1H), 3.69-3.72 (m, 6H), 3.90 (m, 4H), 4.10-4.13 (m, 1H), 4.15-4.22 (m, 4H), 4.39-4.43 (m, 1H), 5.41-5 .42 (m, 2H), 9.27-9.31 (d, 1H); C25H36N10O5S; HPLC 97.3%; mass 590.4 (M+1) 409

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( R)-3-aminopyrrolidin-1-yl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 2.86-2.89 (m, 1H), 3.18-3.20 (m, 1H), 3.22-3.27(m, 2H), 3.55-3.59(m, 9H), 3.64-3.69(m, 1H), 3.71-3.85( m, 4H), 4.13-4.35 (m, 1H), 4.35-4.39 (m, 2H), 4.40-4.43 (m, 1H), 4.82 (m, 1H), 5.4-5.42(m, 3H), 7.21-7.33(m, 1H), 7.41-7.43(m, 1H), 9.27(s, 1H) ; C27H40N10O5S; HPLC 90%; mass 617.4 (M+1) 410

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-(dimethylamino)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.24 (d, 3H), 1.33 (m, 3H), 2.31 (m, 1H), 2.56 (m, 1H), 2.90 (s , 6H), 3.10-3.2 (m, 1H), 3.54-3.6 (m, 1H), 3.59 (m, 2H), 3.71-3.76 (m, 2H ), 3.95 (m, 1H), 4.0 (m, 4H), 4.13-4.16 (m, 2H), 4.40-4.43 (m, 1H), 4.50- 4.80 (m, 1H), 5.30-5.42 (m, 2H), 9.25 (s, 1H); C24H35N9O5S; HPLC 94.55%; mass 562.6 (M+1) 411

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2R,4S )-4-amino-2-methylpyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.77 (d, 3H), 1.79 (d, 6H), 2.46 (m, 1H), 2.70-2.74 (m, 1H), 3 .70-3.73(m, 2H), 3.77(m, 2H), 3.88(m, 1H), 4.03-4.05(m, 2H), 4.08(m, 1H ), 4.13-4.15(m, 1H), 4.21-4.23(m, 1H), 4.33(m, 1H), 4.39-4.41(m, 1H), 4.42-4.65(m, 1H), 4.82-4.90(m, 2H), 5.41-5.42(m, 1H), 9.27(s, 1H); C23H33N9O5S; HPLC 93.8%; mass 548.2 (M+1) 412

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4S )-4-amino-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.29 (d, 3H), 2.94 (m, 2H), 3.32 (m, 2H), 3.57-3 .59 (m, 2H), 3.62-3.65 (m, 2H), 3.96 (m, 1H), 4.07-4.10 (m, 3H), 4.13-4.15 (m, 4H), 4.41 (m, 2H), 5.40-5.42 (m, 2H), 9.25-9.27 (s, 1H); C23H33N9O6S
HPLC 92.7%; mass 564.0 (M+1) 413

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3,4- diaminopyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (3, 3H), 2.96-3.00 (m, 1H), 3.33-3.36 (m, 2H), 3.49 (m, 1H), 3.55-3.58 (m, 1H), 3.61-3.63 (m, 2H), 3.71 (m, 2H), 3.92 -3.97(m, 2H), 4.08(m, 1H), 4.13-4.16(m, 1H), 4.39-4.43(m, 1H), 4.50(m , 1H), 4.82 (m, 1H), 5.42-5.47 (m, 2H), 9.27 (s, 1H); C22H32N10O5S
HPLC 90.6%; mass 549.2 (M+1) 414

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4S )-3-amino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.29 (d, 3H), 1.34 (d, 3H), 1.92 (m, 2H), 3.21-3.31 (m, 1H), 3 .59-3.63 (m, 2H), 3.89-3.92 (m, 4H), 4.00-4.03 (m, 1H), 4.14-4.16 (m, 3H) , 4.40-4.43(m, 1H), 4.61-4.63(m, 2H), 5.41-5.46(m, 2H), 9.27(s, 1H); C22H31N9O6S; HPLC 95%; mass 550.4 (M+1) 415

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(2-aminoethylthio)-4-methyl-7-oxo- 1-azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.14 (d, 3H), 1.28 (d, 3H), 3.01-3.05 (m, 1H), 3.23-3.27 (m, 1H), 3.38-3.40(m, 2H), 3.57-3.59(m, 1H), 3.72(m, 1H), 4.12-4.15(m, 1H) , 4.40-4.43(m, 1H), 4.82(m, 1H), 5.40-5.47(m, 1H), 9.27(s, 1H); C15H21N7O4S; HPLC 90.95; mass 396.3 (M+1) 416

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -hydroxyethyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.92 (m, 1H), 2.55-2.69 (m, 3H) 2, 84-3.01 (m, 4H), 3.32-3.39 (m, 4H), 3.57-3.61 (m, 2H), 3.80-3.83 (m, 2H), 4.00 (m, 2H), 4.13-4.15 (m, 1H), 4.40-4.43 (m, 1H), 4.69-4.71 (m, 1H), 4. 82 (m, 1H), 5.41-5.42 (m, 2H) 9.27 (s, 1H); C24H35N9O6S; HPLC 96.1%; mass 578.2 (M+1) 417

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -amino-2-oxoethyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.86-1.92 (m, 1H), 2.60-2.63 (m, 3H), 3.01-3.18(m, 1H), 3.32-3.36(m, 3H), 3.57-3.62(m, 2H), 3.71-3.99( m, 4H), 4.14-4.16 (m, 1H), 4.40-4.43 (m, 1H), 4.63-4.67 (m, 1H), 4.82 (m, 1H), 5.37-5.42(m, 2H), 7.21-7.23(m, 1H), 7.39-7.43(m, 1H), 9.27(s, 1H) ; C24H34N10O6S; HPLC 96.7%; mass 591.4 (M+1) 418

(4R,5S,6R)-3-((3S,5S)-5-(1,9-diazaspiro[5,5]undecane-9-carbonyl)pyrrolidin-3-ylthio)-6-((R)- 1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.34 (d, 3H), 1.79 (d, 3H), 1.95 (m, 3H), 2.45 (m, 5H), 3.22 (m , 3H), 3.34 (m, 2H), 3.57 (m, 3H), 3.72 (m, 3H), 3.97 (m, 3H), 4.13 (m, 2H), 4 .41 (m, 2H), 5.40-5.42 (m, 2H), 9.27 (s, 1H); C27H39N9O5S; HPLC 93.7%; mass 602.4 (M+1) 419

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(3 -aminopropanoyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.29 (d, 3H), 1.34 (d, 3H), 1.86-1.92 (m, 2H) 2.93 (m, 3H), 3, 28-3.31 (m, 4H), 3.55-3.61 (m, 9H), 4.13-4.15 (m, 1H), 4.59-4.61 (m, 1H), 4.75 (m, 1H), 4.89 (m, 1H), 5.37-5.47 (m, 2H), 9.27 (m, 1H); C25H36N10O6S; HPLC 92.3%; mass 605.3 (M+1) 420

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( S)-2-amino-3-hydroxypropanoyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 3.07-3.21 (m, 1H), 3.36-3.55 (m, 3H), 3.71-3.73(m, 9H), 3.85-3.98(m, 4H), 4.24-4.28(m, 1H), 4.49-4.51( m, 2H), 4.79-4.87 (m, 1H), 5.42 (m, 2H), 9.27 (s, 1H); C25H36N10O7S; HPLC 96.3%; mass 621.2(M+1) 421

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-(2H -1,2,3-triazol-2-yl)azetidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.34 (d, 3H), 2.89 (m, 1H), 3.32-3.36 (m, 2H), 3 .57-3.62 (m, 2H), 3.96 (m, 1H), 4.13-4.16 (d, 1H), 4.42-4.45 (m, 4H), 4.75 -4.82 (m, 3H), 5.3-5.37 (m, 2H), 5.5 (m, 1H), 8.1 (s, 1H), 8.54 (s, 1H), 9.27 (s, 1H); C23H29N11O5S; HPLC 93.5%
Mass 572.2 (M+1) 422

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( 2-aminoacetamido)methyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) 1.29 (d, 3H), 1.34 (d, 3H), 1.82 (m, 4H), 2.47 (m, 1H), 2.79 (m, 1H), 2.94 (m, 1H), 3.2 (m, 2H), 3.34 (m, 1H), 3.57 (m, 4H), 3.76 (m, 4H), 3, 98 (m, 1H), 4.13 (m, 1H), 4.40 (m, 1H), 4.54 (m, 2H), 5.42-5.43 (m, 2H), 9.27 (s, 1H); C26H38N10O6S; HPLC 90%; mass 619.2 (M+1) 423

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(hydroxymethyl )piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 1.83 (m, 6H), 2.84 (m, 1H), 3.0 (m , 1H), 3.32 (m, 1H), 3.48 (m, 1H), 3.57 (m, 2H), 3.70 (m, 1H), 3.78 (m, 3H), 4 .0 (m, 1H), 4.13 (m, 1H), 4.40 (m, 2H), 5.42 (m, 3H), 9.27 (s, 1H); C24H34N8O6S; HPLC 90.2%; mass 563.2 (M+1) 424

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 3-(cyanomethyl)azetidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (3, 3H), 1.85-1.92 (m, 1H), 2.82 (m, 2H), 3 .0 (m, 3H), 3.26 (m, 1H), 3.34 (m, 1H), 3.56 (m, 2H), 3.97 (m, 2H), 4.12-4, 15 (m, 2H), 4.40-4.50 (m, 2H), 5.4 (m, 2H), 9.27 (s, 1H); C23H30N10O5S; HPLC 91.9%; mass 559.2 (M+1) 425

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-amino- 3-fluoropiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.04 (d, 3H), 1.34 (d, 3H) 1.75 (m, 2H), 2.90 (m, 3H), 3.25-3, 34 (m, 5H), 3.56-3.72 (m, 4H), 3.98-3.99 (m, 1H), 4.12-4.14 (m, 1H), 4.40- 4.48 (m, 2H), 5.43 (d, 2H), 9.27 (s, 1H); C23H32FN9O5S; HPLC 92.7%; mass 566.2 (M+1) 426

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(3 -hydroxyazetidin-1-yl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.3 (d, 3H), 1.83-1.85 (m, 2H), 2.82-2.97 (m, 3H), 3.21-3.35(m, 4H), 3.52-3.58(m, 4H), 3.89-3.95(m, 4H), 4.15-4.29( m, 1H), 4.41-4.43 (m, 2H), 4.48-4.51 (m, 1H), 4.58-4.65 (m, 1H), 4.67-4, 68(m, 1H), 4.76-4.83(m, 1H), 5.43(m, 2H), 9.27(s, 1H); C26H37N9O6S; HPLC 96.6%; mass 604.2 (M+1) 427

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4S )-3-guanidino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.82 (m, 2H), 2.85 (m, 1H), 3.35 (m , 1H), 3.63 (m, 3H), 3.74 (m, 3H), 3.89-4.07 (m, 3H), 4.13 (m, 1H), 4.41-4, 45 (m, 2H), 5.42-5.43 (m, 2H), 9.27 (s, 1H); C23H33N11O6S; HPLC 94.1%;
Mass 592.4 (M+1) 428

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( R)-3-aminopyrrolidine-1-carbonyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.30 (d, 3H), 1.45 (m, 2H), 1.92 (m, 4H), 2.38-2 .48 (m, 1H), 2.89-2.93 (m, 3H), 3.28-3.33 (m, 3H), 3.57-3.59 (m, 3H), 3.76 -3.78(m, 4H), 4.0(m, 3H), 4.13(m, 1H), 4.40-4.43(m, 2H), 5.47-5.54(m , 2H), 9.27 (s, 1H); C28H40N10O6S; HPLC 91%; mass 645.6 (M+1) 429

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(3-(piperazin-1-yl)azetidine-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O)-1,20-(d, 3H), 1.34 (d, 3H), 2.7 (m, 3H), 3.24-3.32 (m, 6H), 3.50-3.58(m, 4H), 3.95(m, 1H), 4.13-4.15(m, 2H), 4.18-4.23(m, 4H), 4, 39-4.43 (m, 2H), 5.42-5.47 (m, 3H), 9.27 (s, 1H); C25H36N10O5S; HPLC 90%
Mass 589.3 (M+1) 430

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(4-(piperazine-1-carbonyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.30 (d, 3H), 1.57-1.67 (m, 2H), 1.87-1.90 (m, 3H), 2.9 (m, 2H), 3.1 (m, 1H), 3.26 (m, 5H), 3.5 (m, 4H), 3.83 (m, 2H), 3, 87 (m, 2H), 3.98 (m, 3H), 4.4 (m, 3H), 5.4-5.45 (d, 2H), 9.26 (s, 1H); C28H40N10O6S; mass 644.75 (M+1) 431

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4R )-3-amino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3 H), 1.30 (d, 3H), 2.81 (m, 1H), 3.17 (m, 1H), 3.30- 3.34 (m, 2H), 3.53-3.57 (m, 3H), 3.92-3.93 (m, 2H), 4.12-4.21 (m, 2H), 4. 36-4.40(m, 2H), 4.44-4.55(m, 1H), 4.88(m, 2H), 5.44(m, 2H), 9.24(s, 1H) ; C22H31N9O6S; HPLC 90.6%; mass 550.1 (M+1) 432

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -guanidinoethyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.31 (d, 3H), 1.80-1.82 (m, 1H), 2.55-2.68 (m, 4H), 2.87-2.91(m, 1H), 3.26-3.37(m, 4H), 3.51-3.54(m, 4H), 3.66(m, 2H) , 3.93 (m, 1H), 4.09-4.12 (m, 1H), 4.37-4.40 (m, 1H), 4.49-4.53 (m, 1H), 4 .89 (m, 2H), 5.40 (s, 2H), 9.24 (s, 1H); C25H38N12O5S; HPLC 96.5%; mass 619.2 (M+1) 433

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-amino- 3-fluoropiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.31 (d, 3H), 1.81-1.84 (m, 1H), 2.88-2.90 (m, 2H), 3.27-3.33(m, 4H), 3.42-3.44(m, 1H), 3.48(m, 1H), 3.53-3.54(m, 1H) , 3.69 (m, 2H), 3.92 (m, 1H), 4.09-4.11 (m, 1H), 4.27-4.34 (m, 1H), 4.36-4 .40 (m, 1H), 4.55-4.57 (m, 1H), 4.90 (m, 1H), 5.40 (s, 2H), 9.24 (s, 1H); C23H32FN9O5S; HPLC 93.7%
Mass 566.3 (M+1) 434

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( 2R,4R)-4-aminopyrrolidine-2-carbonyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.30 (d, 3H), 1.90 (m, 2H), 2.66-2.67 (m, 1H), 2 .97-2.98 (m, 1H), 3.11-3.12 (m, 1H), 3.27-3.34 (m, 3H), 3.57-3.58 (m, 2H) , 3.65-3.67 (m, 5H), 3.92-3.95 (m, 2H), 4.09-4.11 (m, 1H), 4.36-4.39 (m, 2H), 4.64-4.65(m, 2H), 4.98(m, 2H), 5.39(s, 2H), 9.23(s, 1H); C27H39N11O6S
HPLC 93%; mass 646.2 (M+1) 435

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(2,8- diazaspiro[4,5]decane-8-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 1.67-1.68 (m, 2H), 1.70-1.71 (m, 2H), 1.82-1.85(m, 1H), 2.94-.297(m, 1H), 3.19-3.20(m, 2H), 3.32-3.35(2H ), 3.37-3.42 (m, 4H), 3.43-3.45 (m, 4H), 3.50-3.53 (m, 1H), 3.54-3.56 (m , 1H), 3.96-3.98 (m, 1H), 4.10-4.11 (m, 1H), 4.37-4.39 (m, 1H), 4.58-4.60 (m, 1H), 5.38-5.40 (m, 2H), 9.24 (s, 1H); C26H37N9O5S; HPLC 90.1%; mass 588.49 (M+1) 436

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(bis(2- hydroxyethyl)carbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.12 (d, 3H), 1.31 (d, 3H), 2.5 (m, 1H), 3.32-3.35 (m, 1H), 3 .42-3.44 (m, 1H), 3.46-3.49 (m, 2H), 3.53-3.56 (m, 2H), 3.57 (m, 2H), 3.59 -3.60 (m, 2H), 3.74-3.95 (m, 1H), 4.11-4.13 (m, 1H), 4.37-4.39 (m, 1H), 4 .41-4.63(m, 1H), 4.80-4.85(m, 1H), 4.85(m, 2H), 5.37-5.40(m, 2H), 9.23 (s, 1H)
C22H32N8O7S; HPLC 90.1%; mass 553.2 (M+1) 437

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( 2-amino-2-oxoethylamino)methyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.17 (d, 3H) 1.31 (d, 3H), 1.86-1.89 (m, 2H), 2.04-2.06 (m, 1H ), 2.82-2.84 (m, 1H), 2.91-2.93 (m, 3H), 3.2-3.24 (m, 1H), 3.29-3.32 (m , 3H), 3.52-3.58 (m, 4H), 3.79-3.80 (m, 3H), 3.95-3.96 (m, 1H), 4.10-4.13 (m, 1H), 4.31-4.38 (m, 2H), 4.57-4.59 (m, 1H), 5.37-5.40 (m, 2H), 9.23 (s , 1H); C26H38N10O6S; HPLC 92.4%; mass 619.4 (M+1) 438

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (d, 3H), 1.97 (m, 1H), 2.12-2.17 (m, 3H), 2 .64 (m, 3H), 3.00-3.07 (m, 3H), 3.27-3.31 (m, 2H), 3.42-3.43 (m, 2H), 3.65 -3.70(m, 3H), 4.01(m, 1H), 4.11-4.13(m, 1H), 4.28-4.30(m, 1H), 4.37-4 .40 (m, 1H), 4.53-4.57 (m, 1H), 5.40 (d, 2H), 9.25 (s, 1H); C25H35N9O5S; HPLC 92.6%; mass 574.4 (M+1) 439

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.30-1.32 (d, 3H), 1.75-1.77 (m, 2H), 2.11-2, 16 (m, 3H), 3.22-3.23 (m, 3H), 3.30-3.36 (m, 2H), 3.40-3.44 (m, 3H), 3.53- 3.55 (m, 2H), 3.79-3.89 (m, 3H), 4.09-4.10 (m, 1H), 4.22-4.27 (m, 1H), 4. 37-4.40 (m, 2H), 5.40 (m, 2H), 9.24 (s, 1H); C25H35N9O5S; HPLC 97.4%; mass 574.2 (M+1) 440

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4R )-4-amino-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.16-1.18 (d, 3H), 1.31-1.32 (d, 3H), 2.24-2.28 (m, 1H), 2, 42-2.49(m, 1H), 2.98(m, 1H), 3.38(m, 2H), 3.62-3.65(m, 4H), 3.76-3.77( m, 2H), 3.87-3.89 (m, 2H), 3.92 (m, 1H), 4.11-4.17 (m, 2H), 4.37-4.40 (m, 2H), 5.39 (s, 2H), 9.24 (s, 1H); C23H33N9O6S; HPLC 94.6%; mass 564.3 (M+1) 441

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4S )-4-amino-2-(methylsulfamido-methyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.17-1.19 (d, 3H), 1.31-1.33 (d, 3H), 1.99-2.02 (m, 2H), 2, 62-2.68 (m, 1H), 2.92-2.97 (m, 2H), 3.09-3.33 (m, 4H), 3.52-3.62 (m, 3H), 3.92 (m, 2H), 4.11-4.13 (m, 2H), 4.28 (m, 1H), 4.37-4.41 (m, 3H), 4.98 (m, 1H), 5.40 (s, 2H), 9.25 (s, 1H); C24H36N10O7S2; HPLC 91.2%; mass 641.2 (M+1) 442

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( S)-3-amino-2-hydroxypropyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.28 (d, 3H), 1.33 (d, 3H), 2.55-2.58 (m, 6H), 2.60-2.63 (m, 2H), 2.93-2.96 (m, 3H), 3.14-3.15 (m, 1H), 3.15-3.18 (m, 3H), 3.51-3.55 ( m, 2H), 3.56-3.58 (m, 2H), 3.95 (m, 1H), 4.12-4.15 (m, 1H), 4.39-4.42 (m, 1H), 4.7 (m, 1H), 5.40-5.42 (m, 2H), 9.26 (s, 1H); C25H38N10O6S; HPLC 96.9%; mass 607.20 (M+1) 443

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( 2-aminoethylamino)methyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (m, 3H), 1.33 (d, 3H), 1.93 (m, 1H), 2.3 (m, 2H), 2.79 (m , 2H), 2.81 (m, 2H), 2.96 (m, 3H), 3.10 (m, 1H), 3.21-3.22 (m, 2H), 3.58-3, 61 (m, 3H), 3.81-3.84 (m, 3H), 4.0 (m, 1H), 4.2 (m, 1H), 4.26-4.28 (m, 2H) , 4.40-4.42(m, 2H), 5.39-5.43(m, 2H), 9.27(s, 1H); C26H40N10O5S; HPLC 90.2%
Mass 605.2 (M+1) 444

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4R )-4-amino-2-(aminomethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 2.23 (m, 1H), 2.40-2.43 (m, 1H), 2 .86 (m, 1H), 3.19-3.27 (m, 4H), 3.50-3.56 (m, 2H), 3.76 (m, 1H), 3.95 (m, 2H ), 4.07-4.13 (m, 2H), 4.35-4.42 (m, 2H), 4.55 (m, 1H), 5.40-5.44 (m, 2H), 9.2 (s, 1H); C23H34N10O5S; HPLC 90.0%; mass 563.4 (M+1) 445

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(3 -aminopropyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (d, 3H), 1.90 (m, 1H), 2.59 (m, 4H), 2.60 (m , 2H), 3.01-3.05 (m, 4H), 3.36-.3.38 (m, 2H), 3.56-3.57 (m, 5H), 3.71 (m, 3H), 4.01-4.05(m, 1H), 4.11-4.13(m, 1H), 4.39(m, 1H), 5.39-5.40(m, 2H) , 9.25 (s, 1H); C25H38N10O5S; HPLC 96.4%; mass 591.4 (M+1) 446

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -guanidinoacetyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.31 (d, 3H), 1.78-1.84 (m, 1H), 2.94-2.95 (m, 1H), 3.28-3.34(m, 2H), 3.53-3.58(m, 5H), 3.62-3.68(m, 4H), 3.95(m, 1H) , 4.09-4.11(m, 2H), 4.23(m, 2H), 4.30-4.38(m, 1H), 4.58(m, 1H), 5.39-5 .43 (m, 2H), 9.24 (s, 1H); C25H36N12O6S
HPLC 93.6%; mass 633.6 (M+1) 447

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4R )-4-amino-2-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3,2, 0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.08 (d, 3H), 1.21 (d, 3H), 2.25 (m, 2H), 2.35-2.44 (m, 2H), 2 .87 (m, 1H), 3.14 (m, 1H), 3.22-3.26 (m, 2H), 3.29-3.30 (m, 2H), 3.43-3.46 (m, 1H), 3.50-3.59 (m, 2H), 3.78 (m, 1H), 3.80-3.86 (m, 3H), 3.93-3.95 (m , 1H), 4.00-4.02 (m, 2H), 4.27-4.29 (m, 2H), 4.82-4.86 (m, 1H), 5.32-5.34 (m, 2H), 9.14 (s, 1H); C27H39N11O6S
HPLC 93.0%; mass 646.4 (M+1) 448

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2H -1,2,3-triazol-2-yl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.17-1.19 (d, 3H), 1.31-1.33 (d, 3H), 2.00-2.07 (m, 2H), 2, 28-2.31(m, 2H), 3.11-3.14(m, 2H), 3.31(m, 1H), 3.45-3.48(m, 2H), 3.55- 3.58 (m, 1H), 3.70-3.80 (m, 1H), 3.85-3.95 (m, 1H), 4.05 (m, 1H), 4.12-4, 14 (m, 1H), 4.38-4.42 (m, 2H), 4.79-4.91 (m, 3H), 5.39-5.40 (s, 2H), 7.78 ( s, 2H), 9.24 (s, 1H); C25H33N11O5S; HPLC 97.4%; mass 600.4 (M+1) 449

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((S)-1-(2-aminoacetyl)pyrrolidine- 3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.27 (d, 3H), 2.3-2.5 (m, 1H), 3.32-3.41 (m, 3H), 3.56-3.60(m, 2H), 3.63-3.88(m, 2H), 3.90-3.96(m, 3H), 4.11-4.15( m, 1H), 4.38-4.42 (m, 1H), 5.40-5.41 (d, 2H), 9.25 (s, 1H); C19H26N8O5S; HPLC 95.3%; mass 479.3 (M+1) 450

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( R)-3-amino-2-hydroxypropyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (m, 3H), 1.89 (m, 2H), 2.54-2.59 (m, 4H), 2 .60-2.62 (m, 2H), 2.90-2.92 (d, 2H), 3.13-3.14 (m, 1H), 3.3 (m, 2H), 3.54 -3.57 (m, 4H), 3.59 (m, 1H), 4.1-4.13 (m, 1H), 4.14 (m, 2H), 4.39 (m, 1H), 4.7 (m, 1H), 5.39-5.40 (m, 2H), 9.25 (s, 1H); C25H38N10O6S; HPLC 90.1%; mass 607.2 (M+1) 451

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(4-(2-(piperazin-1-yl)ethyl)piperazin-1-carbonyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.92 (m, 1H), 2.68-2.76 (m, 6H), 2 .82 (m, 4H), 3.01 (m, 3H), 3.28-3.33 (m, 6H), 3.57-3.59 (m, 6H), 4.00-4.16 (m, 2H), 4.39-4.43 (m, 2H), 5.41-5.42 (m, 2H), 9.27 (s, 1H); C28H43N11O5S; HPLC 92.9%; mass 646.6 (M+1)

The following examples 452-601 were prepared by adapting the preparation method of example 298.

Example Structure Analytical data 452

(4R,5S,6R)-6-((R)-1-(2-(1H-тетразол-1-ил)ацетамидо)этил)-4-метил-3-((3S,5S)-5-(октагидро-1H-пирроло[3,4-b]пиридин-6-карбонил)пирролидин-3-илтио)-7-оксо-1-азабицикло[3,2,0]гепт-2-ен-2-карбоновая кислота

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,4-b]pyridine-6-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 1.77-1.89 (m, 4H), 2.80-2.84 (m, 2H), 2.97-2.99 (m, 1H), 3.11-314 (m, 2H), 3.30-3.34 (m, 3H), 3.43 (m, 1H), 3 .49-3.54 (m, 1H), 3.68-3.71 (m, 1H), 3.77-3.89 (m, 4H), 4.11-4.15 (m, 1H) , 4.24-4.26 (m, 1H), 4.37-4.39 (m, 1H), 5.42-5.44 (d, 2H), 9.24 (s, 1H) C25H35N9O5S HPLC 95.3% mass (M+1) 574.1 453

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4R )-4-amino-2-carboxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 2.06-2.08 (m, 1H), 2.30-2.34 (m, 1H), 2.59-2.61 (m, 2H), 3.03-3.05 (m, 1H), 3.31-3.33 (m, 1H), 3.43-3.48 ( m, 1H), 3.55-3.57 (m, 1H), 3.72-3.77 (m, 2H), 3.94-4.02 (m, 2H), 4.12-4, 14 (m, 1H), 4.37-4.43 (m, 2H), 4.47-4.49 (m, 1H), 5.40-5.44 (d, 2H), 9.24 ( s, 1H)
C23H31N9O7S 25
HPLC 94.8%, wt (M+1) 578.4 454

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4S )-4-amino-2-((sulfamoylamino)-methyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2- en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 1.89-1.96 (m, 1H), 2.59-2.76 (m, 2H), 2.78 (m, 1H), 3.11-3.14 (m, 1H), 3.22-3.29 (m, 2H), 3.41-3.46 (m, 2H) , 3.48-3.49 (m, 1H), 3.54-3.55 (m, 2H), 3.75 (m, 2H), 3.94-4.12 (m, 2H) 4, 29-4.37 (m, 2H), 5.40-5.44 (d, 2H), 9.23 (s, 1H)
C23H35N11O7S2
HPLC 90.1%, wt (M+1) 642.6 455

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4R )-4-amino-2-((sulfamoylamino)methyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene -2-carboxylic acid ¹ H NMR (D ₂ O) 1.17 (d, 3H), 1.30 (d, 3H), 1.88 (m, 1H), 2.22 (m, 1H), 2.33 (m, 1H), 2.42(m, 1H), 2.89(m, 1H), 3.18(m, 1H), 3.20-3.25(m, 1H), 3.30-3.34 (m, 1H), 3.53-3.54 (d, 2H), 3.70-3.77 (m, 2H), 3.86-3.89 (m, 2H) 4.10-4, 11 (m, 2H), 4.28-4.38 (m, 2H), 5.41-5.43 (d, 2H), 9.20 (s, 1H) C23H35N11O7S2
HPLC 90.2% wt (M+1) 642.2 456

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( S)-2,3-diaminoppropanoyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.32 (d, 3H), 1.91 (m, 1H), 2.88-2.91 (m, 2H), 3 .32-3.33 (m, 2H), 3.55-3.57 (m, 2H), 3.61-3.65 (m, 4H), 3.71-3.74 (m, 4H) , 3.80-3.82(m, 1H), 3.96(m, 1H), 4.11-4.13(m, 2H), 4.37-4.41(m, 2H), 5 .42-5.45 (d, 2H), 9.27 (s, 1H) C25H37N11O6S
HPLC 90.2%, wt (M+1) 621.4 457

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( R)-2,3-diaminopropyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (d, 3H), 1.82-1.86 (m, 1H), 1.89 (m, 2H), 2 .72-2.77 (m, 3H), 2.94-2.97 (m, 1H), 3.07-3.10 (m, 1H), 3.23-3.33 (m, 3H) , 3.54-3.56 (m, 3H), 3.70-3.75 (m, 2H), 3.95 (m, 1H), 4.11-4.13 (m, 1H), 4 .37-4.41 (m, 2H), 4.60-4.80 (m, 2H), 5.35-5.45 (m, 2H), 8.43 (m, 1H), 9.23 (s, 1H), C25H39N11O5S
HPLC 90.9%, wt 606.6 (M+1) 458

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(2-( pyrrolidin-1-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.28 (d, 3H), 1.34 (m, 1H), 1.57 (m, 1H), 1.82 (m , 1H), 2.08 (d, 1H), 2.30 (m, 1H), 2.32 (m, 1H), 2.99 (s, 3H), 3.12 (d, 3H), 3 .23-3.24 (d, 2H), 3.32-3.46 (m, 3H), 3.60-3.81 (m, 2H), 4.00 (d, 2H), 4.42 (m, 2H), 4.59 (m, 1H), 4.72 (m, 1H), 5.25 (m, 1H)
C23H35N5O5S
HPLC 90.9%, wt (M+1) 494.6 459

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,4-b]pyridine-6-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.81-1.91 (m, 4H), 2.88 (m, 2H), 3 .16 (m, 1H), 3.20-3.28 (m, 2H), 3.36-3.39 (m, 3H), 3.57-3.59 (m, 2H), 3.72 -3.77(m, 2H), 3.83-3.87(m, 1H), 3.90-3.92(m, 2H), 4.12-4.14(m, 1H), 4 .25-4.29 (m, 1H), 4.39-4.42 (m, 1H), 5.41-5.42 (m, 2H), 9.27 (s, 1H)
C25H35N9O5S
HPLC 96.7%, wt 574.4 (M+1) 460

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 2-(Aminomethyl)morpholine-4-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (d, 3H), 1.89 (m, 1H), 2.72-2.77 (m, 3H), 2 .94-2.97 (m, 1H), 3.07-3.10 (m, 1H), 3.23-3.33 (m, 2H), 3.54-3.56 (m, 2H) , 3.70-3.75(m, 2H), 3.95(m, 1H), 4.11-4.13(m, 1H), 4.37-4.41(m, 2H), 4 .60-4.80 (m, 2H), 5.35-5.45 (m, 2H), 8.43 (m, 1H), 9.23 (s, 1H) C23H33N9O6S
HPLC 90%, wt (M+1) 564.1 461

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((S)- 2-(Aminomethyl)morpholine-4-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (d, 3H), 1.87 (m, 1H), 2.68-2.73 (m, 3H), 2 .90-2.94 (m, 1H), 3.02-3.08 (m, 1H), 3.28-3.42 (m, 2H), 3.58-3.62 (m, 2H) , 3.72-3.78 (m, 2H), 4.01 (m, 1H), 4.14-4.18 (m, 1H), 4.40-4.44 (m, 2H), 4 .72-4.94 (m, 2H), 5.44-5.48 (m, 2H), 8.52 (m, 1H), 9.26 (s, 1H) C23H33N9O6S
HPLC 95.1%, wt (M+1) 564.1 462

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(( S)-3-amino-2-fluoropropyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (d, 3H), 2.58-2.62 (m, 3H), 2.66-2.70 (m, 4H), 2.82-2.87 (m, 2H), 2.93-2.99 (m, 1H), 3.25-3.29 (m, 3H), 3.35-3.39 ( m, 3H), 3.55-3.60 (m, 1H), 3.72-3.99 (m, 1H), 4.0-4.13 (m, 1H), 4.33-4, 65 (m, 1H), 4.67-4.80 (m, 1H), 5.1 (m, 1H), 5.3 (m, 1H), 5.4 (m, 2H), 9.25 (s, 1H)
C25H37FN10O5S
HPLC 95.6%, wt 609.5 (M+1) 463

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(aminomethyl )-4-(hydroxymethyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.27 (d, 3H), 1.33 (d, 3H), 1.65-1.80 (m, 1H), 2.44-2.48 (m, 1H), 3.13-3.14 (m, 1H), 3.30-3.36 (m, 1H), 3.52-3.58 (m, 3H), 3.62-3.65 ( m, 3H), 3.71-3.77 (m, 3H), 3.99 (m, 2H), 4.13-4.15 (m, 3H), 4.31-4.39 (m, 2H), 4.40-4.69 (m, 1H), 4.79 (m, 1H), 5.30-5.46 (m, 2H), 9.25 (s, 1H) C25H37N9O6S
HPLC 90%, wt 591.7 (M+1) 464

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((S)- 2-(aminomethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 1.89-1.96 (m, 1H), 2.42-2.44 (m, 2H) 2.59-2.76 (m, 1H), 2.78 (m, 1H), 3.11-3.14 (m, 1H), 3.22-3.29 (m, 2H), 3.41-3.46(m, 2H), 3.48-3.49(m, 1H), 3.54-3.55(m, 2H), 3.75(m, 2H), 3, 94-4.12 (m, 2H) 4.29-4.37 (m, 2H), 5.40-5.44 (d, 2H), 9.23 (s, 1H) C23H33N9O5S
HPLC 90%, wt (M+1) 548.2 465

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 2-(aminomethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.30 (d, 3H), 1.92 (m, 1H), 2.43-2.46 (m, 2H) 2, 60-2.74 (m, 1H), 2.80-2.82 (m, 1H), 3.14-3.16 (m, 1H), 3.28-3.32 (m, 2H), 3.42-3.45(m, 2H), 3.49-3.51(m, 1H), 3.56-3.58(m, 2H), 3.72-3.78(m, 2H ), 3.90-4.10 (m, 2H) 4.31-4.38 (m, 2H), 5.41-5.43 (d, 2H), 9.23 (s, 1H) C23H33N9O5S
HPLC 95.1%, wt (M+1) 548.2 466

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydropyrrolo[3,4-b]pyrrole-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.3` (d, 3H), 1.92 (m, 1H), 2.01-2.02 (m, 1H), 2.24-2.27(m, 1H), 3.18-3.20(m, 2H), 3.23-3.30(m, 2H), 3.34-3.36(m, 2H ), 3.46-3.48 (m, 3H), 3.65-3.70 (m, 2H), 3.78-3.81 (m, 1H), 3.94-3.96 (m , 1H) 4.12-4.15 (m, 1H), 4.38-4.40 (m, 1H), 4.45-4.49 (m, 1H), 4.68-4.71 ( m, 1H), 5.44-5.46 (d, 2H), 9.25 (s, 1H)
C24H33N9O5S
HPLC 97.9% wt (M+1) 560.2 467

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydropyrrolo[3,4-b]pyrrole-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.32 (d, 3H), 1.94-1.95 (m, 1H), 1.97-1.99 (m, 1H), 2.22-2.26(m, 1H), 3.17-3.19(m, 2H), 3.21-3.29(m, 2H), 3.30-3.31( m, 2H), 3.43-3.47 (m, 3H), 3.64-3.69 (m, 2H), 3.77 (m, 1H), 3.95 (m, 1H) 4, 11-4.14 (m, 1H), 4.37-4.39 (m, 1H), 4.41-4.49 (m, 1H), 4.65-4.66 (m, 1H), 5.42-5.44 (d, 2H), 9.25 (s, 1H) C24H33N9O5S
HPLC 92.7%, wt (M+1) 560.2 468

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)
-4-methyl-3-((3S,5S)-5-(octahydro-1H-pyrrolo[3,2-b]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[ 3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.64-1.68 (m, 2H), 1.81-1.91 (m, 2H), 2.23-2.27(m, 2H), 2.46-2.49(m, 1H), 2.91-3.01(m, 1H), 3.15-3.18( m, 1H), 3.23-3.28 (m, 1H), 3.31-3.48 (m, 2H), 3.58-3.65 (m, 3H), 3.89-3, 96 (m, 3H), 4.12-4.15 (m, 1H), 4.29-4.43 (m, 3H), 5.42-5.44 (d, 2H), 9.27 ( s, 1H)
C25H35N9O5S
HPLC 94.6%, wt (M+1) 574.2 469

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,2-b]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.70-1.93 (m, 4H), 2.14-2.17 (m, 1H), 2.37-2.47(m, 2H), 2.98(m, 1H), 3.21(m, 1H), 3.32-3.35(m, 2H), 3.57 -3.58 (m, 2H), 3.72-3.79 (m, 2H), 3.94-3.98 (m, 2H), 4.13-4.15 (m, 2H), 4 .32-4.44 (m, 3H), 5.42-5.44 (d, 2H), 9.27 (s, 1H)
C25H35N9O5S
HPLC 90%, wt (M+1) 574.2 470

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4S )-2-(aminomethyl)-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 2.03-2.07 (m, 1H), 2.42-2.46 (m, 1H), 2.95-3.00 (m, 1H), 3.33-3.39 (m, 4H), 3.54-3.58 (m, 3H), 3.74-3.77 ( m, 2H), 3.81-3.99 (m, 1H), 4.14-4.16 (m, 1H), 4.33-4.48 (m, 3H), 4.58 (m, 1H), 5.44-5.46 (m, 2H), 9.27 (s, 1H) C23H33N9O6S
HPLC 92.4%, wt (M+1) 564.2 471

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( (4aR,7aS)-octahydropyrrolo[3,4-b][1,4]oxazine-4-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2- en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.81-1.84 (m, 1H), 2.86-2.92 (m, 1H), 3.31-3.34 (m, 2H), 3.37-3.40 (m, 1H), 3.47-3.53 (m, 4H), 3.55-3.62 ( m, 3H), 3.94 (m, 1H), 4.02-4.04 (m, 1H), 4.12-4.14 (m, 1H), 4.31-4.38 (m, 2H), 4.40-4.42(m, 1H), 4.56-4.57(m, 1H), 5.02-5.04(m, 1H), 5.44-5.46( m, 2H), 9.26 (s, 1H) C23H33N9O6S
HPLC 90.3% wt (M+1) 564.1 472

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((S)- 3-(aminomethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.82-1.85 (m, 2H), 2.16-2.30 (m, 1H), 2.4-2.6(m, 1H), 2.93(m, 1H), 3.10-3.13(m, 2H), 3.32-3.33(m, 2H) , 3.56-3.57(m, 2H), 3.63-3.65(m, 1H), 3.71-.379(m, 2H), 3.96(m, 1H), 4, 12-4.14 (d, 2H), 4.40-4.42 (m, 2H), 5.43-5.44 (d, 2H), 9.26 (s, 1H) C23H33N9O5S
HPLC 90.9%, wt 548.3 (M+1) 473

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2R,4R )-4-amino-2-(aminomethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.33 (d, 3H), 1.78-1.80 (m, 1H), 2.42-2.44 (m, 1H), 2.80-2.84 (m, 1H), 3.15-3.18 (m, 2H), 3.30-3.36 (m, 3H), 3.54-3.56 ( m, 2H), 3.70-3.77 (m, 1H), 3.84-3.94 (m, 3H), 4.11-4.12 (m, 1H), 4.23 (m, 1H), 4.30-4.39 (m, 2H), 5.43-5.45 (d, 2H), 9.25 (s, 1H)
C23H34N10O5S
HPLC 90.0% wt (M+1) 563.2 474

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2R,4R )-4-amino-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) 1.19 (d, 3H), 1.32 (d, 3H), 2.4 (m, 1H), 2.78 (m, 1H), 2.88 (m, 1H), 3.22-3.25(m, 2H), 3.31-3.33(m, 1H), 3.4(m, 2H), 3.54-3.56(m, 2H) , 4.0 (m, 2H), 4.3-4.39 (m, 2H), 4.40-4.79 (m, 3H), 5.3-5.4 (m, 3H), 9 .23 (s, 1H) C23H33N9O6S, HPLC 90.5%, wt 564.3 (M+1) 475

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-amino- 4-(hydroxymethyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.31 (d, 3H), 3.30-3.45 (m, 5H), 3.50-3.79 (m, 5H), 4.10-4.18 (m, 4H), 4.30-4.38 (m, 4H), 5.30-5.41 (m, 4H), 9.24 (s, 1H) C24H35N9O6S
HPLC 94%, wt 578.3 (M+1) 476

(4R,5S,6R)-3-((3S,5S)-5-(1,9-diazaspiro[5,5]undecane
1-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-
1-azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.33 (d, 3H), 1.68-1.81 (m, 8H), 1.96-2.0 (m, 1H), 2.98-3.05 (m, 3H), 3.21-3.26 (m, 3H), 3.28-3.30 (m, 2H), 3.41 (m, 2H) , 3.48 (m, 2H), 3.55-3.57 (m, 2H), 4.12-4.15 (m, 2H), 4.40 (m, 1H), 5.40-5 .41 (3, 2H), 9.26 (s, 1H) C27H39N9O5S
HPLC 93.2%, wt (M+1) 602.2 477

(4R,5S,6R)-3-((3S,5S)-5-(1,8-diazaspiro[4,5]decane-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)- 1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.33 (d, 3H), 1.63-1.67 (m, 2H), 1.70-1.73 (m, 2H), 1.81-1.84 (m, 2H), 1.98-2.02 (m, 1H), 3.04-3.12 (m, 3H), 3.24-3.28 ( m, 3H), 3.30-3.36 (m, 2H), 3.44-3.46 (m, 2H), 3.49-3.51 (m, 2H), 3.57-3, 59 (m, 2H), 4.11-4.13 (m, 2H), 4.37-4.40 (m, 1H), 5.42-5.44 (3, 2H), 9.26 ( s, 1H)
C26H37N9O5S
HPLC 95.1%, wt (M+1) 588.6 478

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 4-Fluoropyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 2.42-2.46 (m, 1H), 2.93 (m, 1H), 3 .10-3.13 (m, 2H), 3.32-3.33 (m, 2H), 3.56-3.57 (m, 2H), 3.63-3.65 (m, 1H) , 3.71-.379 (m, 2H), 3.96 (m, 1H), 4.12-4.14 (d, 2H), 4.40-4.42 (m, 2H), 5, 43-5.44 (d, 2H), 9.26 (s, 1H) C22H30FN9O5S
HPLC 97.9%, wt (M+1) 552.1 479

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 4-Fluoropyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.32 (d, 3H), 2.38-2.42 (m, 1H), 2.78-2.89 (m, 1H), 3.12-3.15(m, 2H), 3.34-3.36(m, 2H), 3.62-3.64(m, 2H), 3.66-3.68( m, 1H), 3.74-3.82 (m, 2H), 3.95-3.97 (m, 1H), 4.11-4.13 (d, 2H), 4.42-4, 44 (m, 2H), 5.45-5.46 (d, 2H), 9.26 (s, 1H)C22H30FN9O5S
HPLC 97.9%, wt (M+1) 552.1 480

(4R,5R,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(2 -aminoethyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4,6-dimethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.34 (d, 3H), 1.63-1.67 (m, 2H), 1.70-1.73 (m, 1H), 1.81-1.84 (m, 2H), 1.91 (m, 4H), 2.81-2.84 (m, 1H), 3.03-3.07 (m, 3H) , 3.19-3.21 (m, 1H), 3.30-3.32 (m, 1H), 3.42-3.46 (m, 1H), 3.71-3.73 (m, 1H), 3.75-3.85(m, 2H), 4.03-4.04(m, 1H), 4.12-4.15(m, 1H), 4.33-4.42( m, 2H), 5.41-5.42 (m, 2H), 9.27 (s, 1H)
C25H37N9O5S
HPLC 95.1%, wt 576.3 (M+1) 481

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-7-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2 -en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.33 (d, 3H), 1.92 (m, 1H), 2.85-3.02 (m, 1H), 3 .27-3.35 (m, 2H), 3.55-3.57 (m, 2H), 3.90-4.01 (m, 4H), 4.11-4.13 (m, 1H) , 4.38-4.42(m, 1H), 4.61(m, 1H), 4.75(m, 2H), 4.92-4.93(m, 1H), 5.39-5 .42 (m, 2H), 6.71 (s, 1H), 9.25 (s, 1H)
C24H31N11O5S
HPLC 90.1%, wt 586.3 (M+1) 482

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(decahydro-1, 6-naphthyridine-6-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.65-1.91 (m, 5H), 2.23 (m, 2H), 2 .91-2.98 (m, 1H), 3.17 (m, 3H), 3.30 (m, 3H), 3.51-3.53 (m, 2H), 3.55-3.57 (m, 1H), 3.71-3.83 (m, 2H), 3.96 (m, 1H), 4.12-4.14 (m, 2H), 4.39-4.42 (m , 1H), 4.54-4.62 (m, 1H), 5.42-5.44 (d, 2H), 9.27 (s, 1H) C26H37N9O5S
HPLC 92.3%, wt 588.3 (M+1) 483

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-(3-(piperazin-1-carbonyl)phenylcarbamoyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0] ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.33 (d, 3H), 2.45 (m, 1H), 2.98 (m, 1H), 3.28 (m , 2H), 3.30-3.34 (m, 2H), 3.41 (m, 1H), 3.54-3.57 (m, 2H), 3.77-3.79 (m, 2H ), 3.98 (m, 1H), 4.00 (m, 2H), 4.12-4.13 (m, 2H), 4.29 (m, 1H), 4.38-4.42 ( m, 1H), 5.41-5.42 (d, 2H), 7.32-7.33 (m, 1H), 7.55-7.56 (m, 2H), 7.67 (s, 1H), 9.26 (s, 1H) C29H36N10O6S
HPLC 94.0% wt (M+1) 653.2 484

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(aminomethyl )phenyl-carbamoyl)-pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19(d, 3H), 1.33 (d, 3H), 2.45 (m, 1H), 2.90-2.93 (m, 1H), 3 .26-3.39 (m, 1H), 3.55-3.57 (m, 1H), 3.61-3.65 (m, 1H), 3.72-3.77 (m, 1H) , 3.96 (m, 1H), 4.11-4.18 (m, 1H), 4.23 (s, 1H), 4.33-4.42 (m, 3H), 5.43-5 .44 (d, 2H), 7.47-7.49 (d, 2H), 7.54-7.56 (d, 2H), 9.27 (s, 1H) C25H31N9O5S
HPLC 91.2%, wt (M+1) 570.2 485

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((S)- 3-(Aminomethyl)piperazine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 2.45 (m, 1H), 2.95-2.98 (m, 2H), 3 .00 (m, 2H), 3.10-3.18 (m, 1H), 3.31-3.35 (m, 3H), 3.56-3.58 (d, 2H), 3.71 -3.78 (m, 2H), 3.96 (m, 1H), 4.12-4.15 (m, 2H), 4.24 (m, 1H), 4.41 (m, 2H), 5.41-5.42 (d, 2H), 9.27 (s, 1H) C23H34N10O5S
HPLC 92.4%, wt (M+1) 563.1 486

(4R,5S,6R)-6-((R)-1-(2,2-difluoroacetamido)ethyl)-4-methyl-3-((3S,5S)-5-(octahydro-1H-pyrrolo[3 ,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.33 (d, 3H), 1.80-1.87 (m, 2H), 2.12-2.18 (m, 2H), 2.25(m, 1H), 2.45(m, 1H), 2.64-2.65(m, 1H), 2.93-2.96(m, 1H), 3.31 -3.37(m, 3H), 3.40-3.41(m, 1H), 3.48(m, 1H), 3.50-3.51(m, 1H), 3.53-3 .59 (m, 1H), 3.70-3.72 (m, 1H), 3.93-3.95 (m, 1H), 4.14-4.16 (m, 2H), 4.29 (m, 1H), 4.31-4.38 (m, 1H), 4.43-4.46 (m, 1H), 6.02-6.29 (t, 1H) C24H33F2N5O5S
HPLC 92% mass (M+1) 542.4 487

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(decahydro-1, 6-naphthyridine-6-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.32 (d, 3H), 1.65-1.68 (m, 3H) 1.80-1.87 (m, 2H ), 2.20-2.22 (m, 2H), 2.94-2.97 (m, 1H), 3.12-3.17 (m, 3H), 3.28-3.30 (m , 3H), 3.52-3.54 (m, 2H), 3.56-3.58 (m, 1H), 3.80-3.89 (m, 2H), 3.94-3.98 (m, 1H), 4.14-4.16 (m, 2H), 4.42-4.44 (m, 1H), 4.60-4.64 (m, 1H), 5.43-5 .45 (d, 2H), 9.27 (s, 1H) C26H37N9O5S
HPLC 97.9% wt (M+1) 588.2 488

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(2,7- diazaspiro[4,4]nonane-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.32 (d, 3H), 1.94-1.95 (m, 2H), 1.97-1.99 (m, 2H), 2.22-2.26(m, 1H), 3.17-3.19(m, 2H), 3.21-3.29(m, 2H), 3.30-3.31( m, 2H), 3.43-3.47 (m, 1H), 3.64-3.69 (m, 2H), 3.77 (m, 2H), 3.95 (m, 2H) 4, 11-4.14 (m, 1H), 4.37-4.39 (m, 1H), 4.41-4.49 (m, 1H), 4.65-4.66 (m, 1H), 5.42-5.44 (d, 2H), 9.25 (s, 1H) C25H35N9O5S
HPLC 90% mass (M+1) 574.2 489

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(5-(2 -aminoethyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2- en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.33 (d, 3H), 1.63-1.67 (m, 2H), 1.70-1.73 (m, 2H), 1.81-1.84 (m, 3H), 1.98-2.02 (m, 2H), 3.04-3.12 (m, 3H), 3.24-3.28 ( m, 3H), 3.30-3.36 (m, 2H), 3.44-3.46 (m, 2H), 3.49-3.51 (m, 2H), 3.57-3, 59 (m, 2H), 4.11-4.13 (m, 2H), 4.37-4.40 (m, 1H), 5.42-5.44 (d, 2H), 9.26 ( s, 1H)
C27H40N10O5S
HPLC 95.1% mass (M+1) 617.4 490

(4R,5S,6R)-4-methyl-6-((R)-1-(2-(methylamino)acetamido)ethyl)-3-((3S,5S)-5-(octahydro-1H-pyrrolo[ 3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.33 (d, 3H), 1.80-1.87 (m, 2H), 2.12-2.18 (m, 2H), 2.25(m, 1H), 2.45(m, 1H), 2.64-2.65(m, 1H), 2.93-2.96(m, 1H), 3.31 -3.37(m, 3H), 3.40-3.41(m, 1H), 3.48(m, 1H), 3.50-3.51(m, 1H), 3.53-3 .59 (m, 1H), 3.70-3.72 (m, 1H), 3.90 (s, 3H), 3.98-4.03 (m, 3H), 4.14-4.16 (m, 2H), 4.29 (m, 1H), 4.31-4.38 (m, 1H), 4.43-4.46 (m, 1H) C25H38N6O5S
HPLC 97.9% mass (M+1) 535.1 491

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4S )-4-amino-2-(fluoromethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.82-1.85 (m, 1H), 2.16-2.23 (m, 1H), 2.4-2.6(m, 1H), 2.93(m, 1H), 3.10-3.13(m, 2H), 3.32-3.33(m, 2H) , 3.56-3.57(m, 2H), 3.63-3.65(m, 1H), 3.71-.379(m, 2H), 3.96(m, 1H), 4, 12-4.14 (d, 2H), 4.40-4.42 (m, 2H), 5.43-5.44 (d, 2H), 9.26 (s, 1H) C23H32FN9O5S
HPLC 97.9% wt (M+1) 566.2 492

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-(3-aminopropanamido)pyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.80-1.83 (m, 2H), 2.20-2.23 (m, 1H), 2.66-2.69 (m, 2H), 2.81-2.98 (m, 1H), 3.24-3.29 (m, 3H), 3.33-3.37 ( m, 1H), 3.41-3.48 (m, 1H), 3.52-3.61 (m, 3H), 3.72-3.78 (m, 2H), 3.91-3, 93 (m, 1H), 4.13-4.15 (m, 1H), 4.28 (m, 1H), 4.38-4.41 (m, 2H), 5.41-5.42 ( m, 2H), 9.29 (s, 1H) C25H36N10O6S
HPLC 97% mass (M+1) 605.1 493

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(2,7- diazaspiro[4,4]nonane-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.23 (d, 3H), 1.76-1.77 (m, 1H), 1.93-2.04 (m, 4H), 2.86 (m, 1H), 3.20-3.27 (m, 4H), 3.34-3.37 (m, 3H), 3.40-3.43 (m, 3H) , 3.45-3.48 (m, 1H), 3.51-3.58 (m, 1H), 3.85-3.88 (m, 1H), 4.02-4.04 (m, 1H), 4.27-4.33(m, 2H), 5.30-5.31(m, 2H), 9.26(s, 1H)
C25H35N9O5S
HPLC 97.9 wt% 574.3 (M+1) 494

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4S )-3-amino-4-methoxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.30 (d, 3H), 2.20-2.23 (m, 1H), 2.95 (m, 2H), 3 .20-3.27 (m, 2H), 3.28-3.31 (m, 2H), 3.38-3.40 (m, 2H), 3.43 (s, 3H), 3.44 -3.47(m, 1H), 3.54-3.91(m, 3H), 3.97(m, 1H), 4.13-4.15(m, 2H), 4.39-4 .42 (m, 1H), 4.50-4.52 (m, 1H), 5.42-5.44 (d, 2H), 9.26 (s, 1H) C25H35N9O5S
HPLC 96.2 wt% (M+1) 574.2 495

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[2,3-c]pyridine-6-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.77-1.80 (m, 2H), 2.14-2.20 (m, 2H), 2.65 (m, 1H), 2.98-3.08 (m, 1H), 3.29-3.33 (m, 2H), 3.36-3.37 (m, 1H) , 3.39-3.49(m, 2H), 3.52(m, 1H), 3.58-3.69(m, 2H), 3.71(m, 2H), 3.88(m , 1H), 3.99-4.05 (m, 3H), 4.12-4.15 (d, 1H), 4.38-4.40 (m, 1H), 5.40-5.41 (d, 2H), 9.26 (s, 1H)
C25H35N9O5S
HPLC 95.8 wt% (M+1) 574.3 496

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 3-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.18 (d, 3H), 2.01-2.24 (m, 2H), 2.98 (m, 1H), 3 .20-3.23 (m, 2H), 3.46-3.47 (m, 2H), 3.50-3.51 (m, 2H), 3.58-3.65 (m, 3H) , 3.68-3.73(m, 2H), 3.86(m, 1H), 4.02-4.04(m, 1H), 4.28-4.32(m, 2H), 5 .30-5.31 (d, 2H), 9.16 (s, 1H) C23H33N9O6S
HPLC 99% mass (M+1) 564.6 497

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 3-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 2.21-2.25 (m, 2H), 2.96-2.98 (m, 1H), 3.22-3.25(m, 2H), 3.47-3.49(m, 2H), 3.51-3.54(m, 2H), 3.59-3.65( m, 3H), 3.71-3.76 (m, 2H), 3.92-3.96 (m, 1H), 4.04-4.06 (m, 1H)6 4.30-4, 34 (m, 2H), 5.32-5.33 (d, 2H), 9.25 (s, 1H)
C23H33N9O6S
HPLC 90.3% mass (M+1) 564.2 498

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4R )-3-amino-4-fluoropyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.23 (d, 3H), 1.81 (m, 1H), 2.89-2.92 (m, 2H), 3 .23-3.28(m, 2H), 3.29(m, 2H), 3.46-3.48(m, 2H), 3.51-3.53(m, 2H), 3.83 -3.89 (m, 3H), 4.02-4.04 (m, 1H), 4.28-4.32 (m, 1H), 5.30-5.31 (d, 2H), 9 .16 (s, 1H)
C22H30FN9O5S HPLC 99%
Mass (M+1) 552.2 499

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(2,8- diazaspiro[4,5]decane-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.34 (d, 3H), 1.85-1.97 (m, 5H), 2.03-2.04 (m, 3H), 2.91-2.97(m, 1H), 3.27-3.37(m, 6H), 3.42-3.46(m, 1H), 3.51-3.58( m, 4H), 3.72 (m, 1H), 4.13-4.15 (m, 1H), 4.40-4.41 (m, 2H), 5.42-5.47 (d, 2H), 9.27 (s, 1H)
C26H37N9O5S
HPLC 98.8% mass (M+1) 588.1 500

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-(2-aminopropan-2-yl)pyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (m, 9H), 2.21-2.25 (m, 2H), 2.96-2.98 (m, 1H), 3.22-3.25(m, 2H), 3.47-3.49(m, 2H), 3.51-3.54(m, 2H), 3.59-3.65( m, 3H), 3.71-3.76 (m, 1H), 3.92-3.96 (m, 1H), 4.04-4.06 (m, 1H) 4.30-4.34 (m, 2H), 5.32-5.33 (d, 2H), 9.25 (s, 1H)
C25H37N9O5S
HPLC 97.9% wt (M+1) 576.3 501

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(2,6- diazaspiro[3,4]octane-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.23 (d, 3H), 1.76-1.77 (m, 1H), 1.93-2.04 (m, 2H), 2.86 (m, 1H), 3.20-3.27 (m, 4H), 3.34-3.37 (m, 3H), 3.40-3.43 (m, 3H) , 3.45-3.48 (m, 1H), 3.51-3.58 (m, 1H), 3.85-3.88 (m, 1H), 4.02-4.04 (m, 1H), 4.27-4.33 (m, 2H), 5.30-5.31 (d, 2H), 9.26 (s, 1H)
C24H33N9O5S
HPLC 97.9% wt (M+1) 560.4 502

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(2,6- diazaspiro[3,4]octane-6-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.88 (m, 1H), 2.02-2.04 (m, 2H), 2 .84-2.86 (m, 1H), 3.22-3.29 (m, 4H), 3.35-3.38 (m, 3H), 3.41-3.44 (m, 3H) , 3.46-3.49 (m, 1H), 3.52-3.59 (m, 1H), 3.86-3.89 (m, 1H), 4.03-4.05 (m, 1H), 4.28-4.34 (m, 2H), 5.31-5.32 (d, 2H), 9.26 (s, 1H) C24H33N9O5S
HPLC 90% mass (M+1) 560.4 503

(4R,5S,6R)-3-((3S,5S)-5-(1,7-diazaspiro[4,5]decane-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)- 1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.90-1.95 (m, 5H), 2.01-2.03 (m, 3H), 2.89-2.92(m, 1H), 3.29-3.34(m, 6H), 3.41-3.47(m, 1H), 3.52-3.55( m, 4H), 3.69-3.72 (m, 1H), 4.11-4.14 (m, 1H), 4.39-4.40 (m, 2H), 5.41-5, 45 (d, 2H), 9.27 (s, 1H) C26H37N9O5S HPLC 95.1%
Mass (M+1) 588.2 504

(4R,5S,6R)-3-((3S,5S)-5-(1,7-diazaspiro[4,5]decane-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)- 1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.92-1.97 (m, 5H), 2.02-2.04 (m, 3H), 2.91-2.94 (m, 1H), 3.30-3.35 (m, 6H), 3.42-3.48 (m, 1H), 3.53-3.56 ( m, 4H), 3.72-3.75 (m, 1H), 4.12-4.15 (m, 1H), 4.40-4.41 (m, 2H), 5.42-5, 46 (d, 2H), 9.27 (s, 1H) C26H37N9O5S
HPLC 97.9% mass (M+1) 588.2 505

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydropyrrolo[3,4-b]pyrrole-5-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.82-1.87 (m, 2H), 1.92-2.01 (m, 2H), 2.33-2.39 (m, 2H), 2.94-2.98 (m, 2H), 3.28-3.34 (m, 2H), 3.44-3.47 ( m, 3H), 3.50-3.52 (m, 1H), 3.72-3.77 (m, 1H), 3.89-3.93 (m, 2H), 4.13-4, 15 (m, 1H), 4.40-4.43 (m, 2H), 5.43-5.47 (d, 2H), 9.27 (s, 1H) C24H33N9O5S
HPLC 93.1% mass (M+1) 560.4 506

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydropyrrolo[3,4-b]pyrrole-5-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.32 (d, 3H), 1.85-1.91 (m, 2H), 2.01-2.03 (m, 2H), 2.35-2.41(m, 2H), 2.98-3.01(m, 2H), 3.30-3.36(m, 2H), 3.46-3.49( m, 3H), 3.52-3.54 (m, 1H), 3.74-3.79 (m, 1H), 3.91-3.95 (m, 2H), 4.14-4, 16 (m, 1H), 4.42-4.45 (m, 2H), 5.44-5.48 (d, 2H), 9.27 (s, 1H) C24H33N9O5S HPLC 90%
Mass (M+1) 560.4 507

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(difluoromethylthio)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.32 (d, 3H), 1.92-1.95 (m, 1H), 1.97-2.00 (m, 1H), 2.19-2.32(m, 1H), 2.46-2.50(m, 1H), 2.94-2.96(m, 1H), 3.30-3.37( m, 2H), 3.51-3.56 (m, 1H), 3.58-3.59 (m, 2H), 3.61-3.64 (m, 2H), 3.72-3, 77 (m, 1H), 3.88-3.96 (m, 2H), 4.07-4.12 (m, 2H), 4.35-4.39 (m, 2H), 6.96- 7.23 (t, 1H)
C22H31F2N5O5S2
HPLC 90.7% mass (M+1) 548.1 508

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-((R)-1-(2-( piperazin-1-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.27 (d, 3H), 1.37 (d, 3H), 1.91-1.96 (m, 2H), 2.31-2.33 (m, 1H), 2.59-2.60 (m, 1H), 2.94-3.26 (m, 1H), 2.99 (s, 3H), 3.07 (s, 3H), 3.21 .3.22 (m, 1H), 3.40-3.45 (m, 2H), 3.47-3.49 (m, 4H), 3.57-3.58 (m, 2H), 3 .73-3.77 (m, 2H), 3.91 (m, 1H), 4.13-4.15 (m, 1H), 4.43-4.47 (m, 2H) C23H36N6O5S HPLC 97, 9% mass (M+1) 509.3 509

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidin-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-6-( (R)-1-(2-((S)-pyrrolidin-2-yl)acetamido)ethyl)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.80-1.85 (m, 1H), 2.08-2.13 (m, 1H), 2.19-2.32(m, 1H), 2.44-2.48(m, 3H), 2.70-3.00(m, 3H), 2.94-2.96( m, 1H), 3.19 (d, 3H), 3.29-3.37 (m, 3H), 3.40-3.45 (m, 2H), 3.47-3.49 ( m, 4H), 3.54-3.78 (m, 2H), 4.14 (d, 1H), 4.38-4.42 (m, 1H), C25H38N6O5S HPLC 97.9%
Mass (M+1) 535.1 510

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-(aminomethyl )-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.34 (d, 3H), 1.82-1.85 (m, 2H), 2.18-2.32 (m, 1H), 2.42-2.56 (m, 1H), 2.88-2.93 (m, 1H), 3.11-3.14 (m, 1H), 3.33-3.34 ( m, 2H), 3.57-3.58 (m, 2H), 3.64-3.66 (m, 1H), 3.72-.38 (m, 2H), 3.98-3.99 (m, 1H), 4.13-4.15 (d, 2H), 4.41-4.43 (m, 2H), 5.44-5.45 (d, 2H), 9.27 (s , 1H)
C23H33N9O6S HPLC 90%
Mass (M+1) 564.2 511

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-(aminomethyl )-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.30 (d, 3H), 1.84-1.87 (m, 2H), 2.16-2.30 (m, 1H), 2.40-2.54 (m, 1H), 2.86-2.91 (m, 1H), 3.09-3.12 (m, 1H), 3.31-3.32 ( m, 2H), 3.52-3.53 (m, 2H), 3.62-3.64 (m, 1H), 3.70-.36 (m, 2H), 3.95-3.96 (m, 1H), 4.11-4.13 (d, 2H), 4.38-4.40 (m, 2H), 5.41-5.42 (d, 2H), 9.27 (s , 1H)
C23H33N9O6S HPLC 95.1%
Mass (M+1) 564.2 512

(4R,5S,6R)-6-((R)-1-(2-(3,3-difluoropyrrolidin-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(dimethylcarbamoyl) pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.33 (d, 3H), 1.8-1.86 (m, 2H), 1.91-1.96 (m, 2H), 2.14-2.20 (m, 2H), 2.31-2.33 (m, 1H), 2.59-2.60 (m, 1H), 2.95-296 (m, 1H), 2.99 (s, 3H), 3.07 (s, 3H), 3.21,3.22 (m, 1H), 3.40-3.45 (m, 2H), 3.73 -3.77 (m, 2H), 3.91 (m, 1H), 4.13-4.15 (m, 1H), 4.43-4.47 (m, 2H) C23H33F2N5O5S HPLC 97.9% mass 530.1 (M+1) 513

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-((3S,5S) -5-((R)-pyrrolidin-3-ylmethylcarbamoyl)pyrrolidin-3-ylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.32 (d, 3H), 1.85-1.88 (m, 2H), 2.18-2.32 (m, 1H), 2.42-2.46 (m, 1H), 2.89-2.93 (m, 1H), 3.12-3.15 (m, 2H), 3.33-3.34 ( m, 2H), 3.57-3.58 (m, 2H), 3.63-3.65 (m, 1H), 3.71-.379 (m, 2H), 3.96 (m, 1H ), 4.12-4.14 (d, 2H), 4.40-4.42 (m, 2H), 5.43-5.44 (d, 2H), 9.26 (s, 1H) C23H33N9O5S HPLC 97.9% mass (M+1) 548.3 514

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(( Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept -2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 9H), 1.79-1.82 (m, 1H), 2.08-2.11 (m, 1H), 2.35-2.38(m, 1H), 3.33-3.40(m, 1H), 3.67-3.71(m, 1H), 3.73(m, 1H) , 3.78 (d, 2H), 3.90 (m, 1H), 4.12-4.14 (m, 2H), 4.14-4.15 (m, 2H), 4.16 (d , 1H), 4.41 (d, 1H), 4.60 (d, 1H), 4.84 (d, 1H), 8.54 (s, 1H), C28H38N8O8S2
HPLC 90% mass (M+1) 679.1 515

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(1-carbamimidoylazetidin-3-ylthio)-4-methyl- 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.28 (d, 3H), 1.34 (d, 3H), 2.86 (m, 1H), 3.02-3.06 (m, 1H), 3 .44-3.48(m, 1H), 3.57-3.60(m, 1H), 3.73-3.77(m, 1H), 4.05(m, 2H), 4.27 -4.33 (m, 2H), 5.42 (d, 2H), 9.27 (s, 1H)
C17H23N9O4S
HPLC 95.1% mass (M+1) 450.4 516

(4R,5S,6R)-3-((3S,5S)-5-(1,4-diazepan-1-carbonyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-( 1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.85-1.92 (m, 1H), 2.94-3.26 (m, 4H), 3.46-3.49 (m, 4H), 3.57-3.58 (m, 2H), 3.62-3.72 (m, 1H), 3.73-3.76 ( m, 1H), 3.80-3.84 (m, 2H), 3.87-3.92 (m, 1H), 3.94-4.13 (m, 1H), 4.30 (d, 1H), 4.43-4.49(m, 1H), 4.51-4.53(m, 1H), 5.47(m, 2H), 9.27(s, 1H)
C23H33N9O5S HPLC 97.9 wt% (M+1) 548.1 517

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-carbamimidoyl- 1,4-diazepan-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) 1.20 (d, 3H), 1.34 (d, 3H), 1.88-1.95 (m, 1H), 3.12-3.34 (m, 4H ), 3.48-3.51 (m, 4H), 3.59-3.60 (m, 2H), 3.64-3.74 (m, 1H), 3.75-3.78 (m , 1H), 3.82-3.86 (m, 2H), 3.88-3.93 (m, 1H), 4.12-4.15 (m, 1H), 4.38 (d, 1H ), 4.48-4.52 (m, 1H), 4.58-4.60 (m, 1H), 5.48 (m, 2H), 9.27 (s, 1H) C24H35N11O5S
HPLC 97.9% mass (M+1) 590.2 518

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-(2-(2-methoxyethylamino)acetamido)ethyl) -4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.29 (d, 3H), 1.94-2.0 (m, 1H), 3.00 (s, 3H), 3 .03 (s, 3H), 3.28 (s, 3H), 3.35-3.37 (m, 1H), 3.41 (s, 3H), 3.57-3.58 (m, 1H ), 3.60-3.62 (m, 2H), 3.72-3.73 (m, 3H), 3.90-3.91 (m, 2H), 4.03-4.04 (m , 1H), 4.14-4.16 (m, 1H), 4.44-4.47 (m, 1H)
C22H35N5O6S HPLC 95.3 wt% (M+1) 498.2 519

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((1R)-1-(2-(octahydro-1H- pyrrolo[3,2-c]pyridin-1-yl)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.31 (d, 3H), 1.57-1.65 (m, 1H), 1.92-2.00 (m, 2H), 2.08-2.10 (m, 2H), 2.55-2.59 (m, 1H), 2.95 (m, 1H), 3.00 (s, 3H), 3.04 (m, 1H), 3.07 (s, 3H), 3.11-3.19 (m, 2H), 3.23-3.26 (m, 2H), 3.34-3.39 (m , 3H), 3.40-3.43(m, 2H), 3.48(m, 1H), 3.68-3.70(m, 2H), 4.02-4.09(m, 1H ), 4.19-4.21 (m, 1H), 4.33 (m, 1H), 4.72-4.74 (m, 1H) C26H40N6O5S
HPLC 97.5% mass (M+1) 549.1 520

(4R,5S,6R)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-4-methyl-6-((R)-1-(2-((S)- 2-((methylamino)methyl)pyrrolidin-1-yl)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.19 (d, 3H), 1.54-1.57 (m, 1H), 1.63-1.67 (m, 1H), 1.88 (m, 2H), 1.98-2.01 (m, 1H), 2.36-2.40 (m, 1H), 2.62 (s, 3H), 2.87 (m, 1H), 2.94 (s, 3H), 3.01 (m, 1H), 3.03 (s, 3H), 3.09 (m, 1H), 3.13 (m, 2H) , 3.24(m, 1H), 3.34(m, 3H), 3.46(m, 2H), 3.75-3.85(m, 1H), 4.03-4.05(m , 1H), 4.29-4.33 (m, 1H), 4.49 (m, 1H) C25H40N6O5S
HPLC 93.1% mass (M+1) 537.2 521

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(5-(( S)-3-amino-2-hydroxypropyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3, 2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.22 (d, 3H), 1.71-1.79 (m, 2H), 1.92-1.98 (m, 2H), 2.11 (m, 2H), 2.50 (m, 2H), 2.72 (m, 1H), 2.79-2.81 (m, 1H), 2.84-2.86 (m, 2H), 2.97 (m, 1H), 3.03-3.06 (m, 2H), 3.20-3.22 (m, 3H), 3.44-3.54 (m , 3H), 3.65 (m, 1H), 3.73-3.78 (m, 1H), 3.85 (m, 1H), 4.00-4.03 (m, 1H), 4, 16 (m, 1H), 4.27-4.30 (m, 1H), 5.30-5.34 (d, 2H), 9.15 (s, 1H) C28H42N10O6S HPLC 99.8% wt (M +1) 647.3 522

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,3R )-3-amino-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.22 (d, 3H), 1.82-1.86 (m, 1H), 2.03-2.08 (m, 1H), 2.31-2.33(m, 1H), 2.46-2.48(m, 1H), 2.77-2.82(m, 1H), 3.18-3.23( m, 2H), 3.38-3.39 (m, 2H), 3.58-3.61 (m, 1H), 3.65-3.68 (m, 2H), 3.82-3, 87 (m, 2H), 4.00-4.02 (m, 1H), 4.11 (m, 1H), 4.28-4.29 (m, 2H), 5.26-5.28 ( d, 2H), 9.13 (s, 1H) C23H33N9O6S
HPLC 91.7% wt (M+1) 564.2 523

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,3R )-3-amino-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.06 (d, 3H), 1.20 (d, 3H), 1.74-1.78 (m, 1H), 2.05-2.08 (m, 1H), 2.44-2.49 (m, 1H), 2.75-2.78 (m, 1H), 3.08-3.19 (m, 1H), 3.20-3.23 ( m, 1H), 3.31-3.35 (m, 1H), 3.43-3.44 (m, 1H), 3.55-3.59 (m, 1H), 3.63-3, 69 (m, 2H), 3.72-3.79 (m, 1H), 3.85 (m, 1H), 3.99 (m, 1H), 4.01 (m, 1H), 4.13 (m, 1H), 4.26-4.29 (m, 2H), 5.28-5.29 (d, 2H), 9.13 (s, 1H) C23H33N9O6S
HPLC 90.5 wt% (M+1) 564.2 524

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3aR,6aR )-3a-(hydroxymethyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2- en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.06 (d, 3H), 1.20 (d, 3H), 1.78 (m, 1H), 2.74 (m, 1H), 2.86 (m , 1H), 3.11-3.19 (m, 3H), 3.21-3.29 (m, 2H), 3.37-3.39 (m, 3H), 3.50 (m, 2H ), 3.53-3.56 (m, 2H), 3.62 (m, 1H), 3.71-3.77 (m, 2H), 3.99-4.01 (m, 1H), 4.19-4.29 (m, 2H), 5.28-5.33 (d, 2H), 9.26 (s, 1H) C25H35N9O6S
HPLC 92.2% mass (M+1) 590.1 525

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3aS,6aS )-3a-(hydroxymethyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2- en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.27 (d, 3H), 1.80 (m, 1H), 2.76 (m, 1H), 2.88 (m , 1H), 3.18-3.26 (m, 3H), 3.26-3.34 (m, 2H), 3.39-3.41 (m, 3H), 3.52 (m, 2H ), 3.55-3.58 (m, 2H), 3.64 (m, 1H), 3.74-3.80 (m, 2H), 4.02-4.03 (m, 1H), 4.22-4.32 (m, 2H), 5.30-5.35 (d, 2H), 9.27 (s, 1H) C25H35N9O6S
HPLC 97.9% wt (M+1) 589.67 526

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3aS,5S ,6aS)-5-amino-3a-(hydroxymethyl)octahydrocyclopenta[c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept- 2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.21 (d, 3H), 1.69-1.79 (m, 2H), 1.93-1.95 (m, 2H), 2.11-2.16(m, 1H), 2.59-2.82(m, 2H), 3.16-3.19(m, 3H), 3.20-3.27( m, 1H), 3.32-3.48 (m, 3H), 3.52-3.59 (m, 2H), 3.72 (m, 2H), 3.82 (m, 1H), 4 .00-4.02 (m, 1H), 4.25-4.28 (m, 2H), 5.29-5.30 (m, 2H), 9.14 (s, 1H)
C26H37N9O6S HPLC 92.1%
Mass (M+1) 604.2 527

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,4-c]pyridine-2-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.06 (d, 3H), 1.22 (d, 3H), 1.41-1.48 (m, 1H), 1.63-1.72 (m, 1H), 1.89 (m, 1H), 2.50-2.56 (m, 2H), 2.91-2.97 (m, 2H), 3.02-3.07 (m, 2H) , 3.21 (m, 2H), 3.32-3.35 (m, 2H), 3.41-3.42 (m, 1H), 3.45-3.46 (m, 2H), 3 .67-3.71 (m, 1H), 3.87 (m, 1H), 3.98-4.00 (m, 1H), 4.26-4.29 (m, 1H), 5.29 -5.33 (d, 2H), 9.13 (s, 1H) C24H33N9O6S
HPLC 100% mass 574.1 (M+1) 528

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,4-c]pyridine-2-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.23 (d, 3H), 1.67 (m, 1H), 1.89 (m, 1H), 2.51-2 .69 (m, 2H), 2.86 (m, 1H), 3.05-3.07 (m, 2H), 3.21-3.24 (m, 1H), 3.31-3.39 (m, 3H), 3.46 (m, 1H), 3.54-3.55 (m, 2H), 3.68-3.71 (m, 2H), 3.86 (m, 1H), 4.01-4.03 (m, 1H), 4.29-4.34 (m, 2H), 5.30-5.34 (d, 2H), 9.15 (s, 1H)
C25H35N9O5S HPLC 99.8%
Mass (M+1) 574.1 529

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3aR,5R ,6aR)-5-amino-3a-(hydroxymethyl)octahydrocyclopenta[c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept- 2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.06 (d, 3H), 1.20 (d, 3H), 1.72-1.78 (m, 2H), 1.94 (m, 2H), 2 .11 (m, 1H), 2.56-2.83 (m, 3H), 3.19-3.27 (m, 3H), 3.30-3.47 (m, 3H), 3.57 (m, 3H), 3.73 (m, 1H), 3.83 (m, 2H), 4.01 (m, 1H), 4.29 (m, 1H), 5.28 (d, 2H) , 9.13 (s, 1H)
C26H37N9O6S HPLC 98.6%
Mass (M+1) 604.2 530

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(7-amino- 5-oxa-2-azaspiro[3,4]octane-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.33 (d, 3H), 2.36-2.39 (m, 1H), 2.79-2.85 (m, 2H), 3.28-3.35(m, 2H), 3.57-3.58(m, 2H), 3.95(m, 1H), 4.05-4.07(m, 2H) , 4.13-4.17(m, 3H), 4.27(m, 2H), 4.30-4.32(m, 2H), 4.38-4.39(m, 2H), 5 .41-5.42 (3, 2H), 9.27 (s, 1H) C24H33N9O6S
HPLC 97.3% mass (M+1) 576.4 531

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(7-amino- 5-oxa-2-azaspiro[3,4]octane-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid ¹ H NMR (D ₂ O) -1.21 (d, 3H), 1.34 (d, 3H), 2.38-2.41 (m, 1H), 2.81-2.87 (m, 2H), 3.30-3.37(m, 2H), 3.59-3.60(m, 2H), 3.97-3.99(m, 1H), 4.07-4.09( m, 2H), 4.15-4.19 (m, 3H), 4.29 (m, 2H), 4.32-4.34 (m, 2H), 4.40-4.41 (m, 2H), 5.43-5.44 (3, 2H), 9.27 (s, 1H) C24H33N9O6S HPLC 99.3 wt% (M+1) 576.4 532

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(5-(( S)-3-amino-2-hydroxypropyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3, 2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.80-1.82 (m, 3H), 2.11-2.23 (m, 3H), 2.62-2.92(m, 3H), 2.97-3.17(m, 3H), 3.20-3.33(m, 3H), 3.35-3.42( m, 2H), 3.52-3.58 (m, 3H), 3.72 (m, 2H), 3.99 (m, 1H), 4.13-4.15 (m, 2H), 4 .32-4.43 (m, 2H), 5.42-5.43 (m, 2H), 9.27 (s, 1H) C28H42N10O6S HPLC 95.2% wt (M+1) 647.1 533

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,4-c]pyridine-5-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.92-1.94 (m, 3H), 2.69 (m, 3H), 3 .09-3.16 (m, 3H), 3.24-3.32 (m, 3H), 3.42-3.45 (m, 3H), 3.50-3.58 (m, 2H) , 3.70-3.75(m, 2H), 4.00(m, 1H), 4.14-4.16(m, 1H), 4.39-4.43(m, 1H), 5 .42-5.43 (d, 2H), 9.27 (s, 1H) C25H35N9O5S HPLC 92.6 wt% (M+1) 574.3 534

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)-ethyl)-3-((3S,5S)-5-(3a-( hydroxymethyl)octahydro-1H-pyrrolo[3,4-c]pyridine-5-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene -2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.92-1.95 (m, 2H), 2.67 (m, 3H), 2 .98-3.07 (m, 2H), 3.23-3.26 (m, 2H), 3.32-3.29 (m, 3H), 3.51-3.59 (m, 3H) , 3.62-3.66(m, 2H), 3.71(m, 2H), 3.90(m, 1H), 4.13-4.15(m, 1H), 4.41-4 .43 (m, 1H), 5.41-5.42 (m, 2H), 9.27 (s, 1H) C25H35N9O5S HPLC 98.9 wt% (M+1) 574.3 535

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3a-(hydroxymethyl )octahydro-1H-pyrrolo[3,4-c]pyridine-5-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.76-1.86 (m, 2H), 2.00 (m, 1H), 2 .97-2.99 (m, 3H), 3.15-3.21 (m, 3H), 3.34-3.49 (m, 5H), 3.52-3.73 (m, 6H) , 3.98 (m, 1H), 4.13-4.15 (m, 1H), 4.40-4.41 (m, 1H), 5.42-5.43 (m, 2H), 9 .27 (s, 1H) C26H37N9O6S HPLC 97.8 wt% (M+1) 604.2 536

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5R)-5-(2-(( R)-3-aminopyrrolidin-1-yl)-2-oxoethyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.34 (d, 3H), 1.81 (m, 1H), 2.09-2.12 (m, 1H), 2 .47 (m, 2H), 2.81 (m, 2H), 3.05 (m, 2H), 3.37-3.40 (m, 2H), 3.60-3.77 (m, 3H ), 3.95 (m, 2H), 4.04-4.09 (m, 2H), 4.13 (m, 1H), 4.41 (m, 1H), 5.42-5.43 ( m, 2H), 9.27 (s, 1H) C23H33N9O5S HPLC 90.2 wt% (M+1) 548.1 537

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydro-1H-pyrrolo[3,4-c]pyridine-5-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.33 (d, 3H), 1.74-1.84 (m, 2H), 1.98 (m, 1H), 2 .95-2.97 (m, 3H), 3.13-3.19 (m, 3H), 3.33-3.47 (m, 5H), 3.50-3.71 (m, 6H) , 3.96 (m, 1H), 4.11-4.13 (m, 1H), 4.38-4.39 (m, 1H), 5.40-5.41 (m, 2H), 9 .25 (s, 1H) C26H37N9O6S HPLC 90.3 wt% (M+1) 604.3 538

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3aR,5S ,6aS)-5-amino-3a-(aminomethyl)octahydro-cyclopenta[c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0] hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.21 (d, 3H), 1.74-1.80 (m, 2H), 1.96 (m, 2H), 2 .13 (m, 1H), 2.58-2.85 (m, 3H), 3.21-3.29 (m, 3H), 3.32-3.49 (m, 3H), 3.59 (m, 3H), 3.75 (m, 1H), 3.85 (m, 2H), 4.03 (m, 1H), 4.31 (m, 1H), 5.30 (d, 2H) , 9.15 (s, 1H) C26H38N10O5S HPLC 90 wt% (M+1) 603.1 539

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3a-(hydroxymethyl )octahydro-1H-pyrrolo[3,4-c]pyridine-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.31 (d, 3H), 1.73-1.83 (m, 2H), 1.87 (m, 1H), 2 .94-2.96 (m, 3H), 3.12-3.18 (m, 3H), 3.31-3.46 (m, 5H), 3.49-3.70 (m, 6H) , 3.95 (m, 1H), 4.10-4.12 (m, 1H), 4.37-4.38 (m, 1H), 5.39-5.40 (m, 2H), 9 .24 (s, 1H) C26H37N9O6S HPLC 95.1% wt (M+1) 604.3 540

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-((3S,5S)-5-( octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.05 (d, 3H), 1.19 (d, 3H), 1.76 (m, 1H), 2.72 (m, 1H), 2.84 (m , 1H), 3.09-3.17 (m, 3H), 3.19-3.27 (m, 2H), 3.35-3.37 (m, 3H), 3.48 (m, 2H ), 3.51-3.54 (m, 2H), 3.60 (m, 1H), 3.69-3.75 (m, 2H), 3.97-3.99 (m, 1H), 4.17-4.27 (m, 2H), 5.26-5.31 (d, 2H), 9.24 (s, 1H) C24H33N9O5S HPLC 97.9% wt 574.3 (M+1) 560 ,four 541

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((1R, 7S )-3,8-Diaza-tricyclo[5.2.1.01.5]decane-3-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0 ]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.23 (d, 3H), 1.74 (m, 1H), 1.81 (m, 4H), 2.46 (m , 1H), 2.86 (m, 1H), 3.15-3.18 (m, 1H), 3.25-3.32 (m, 4H), 3.48 (m, 3H), 3, 75-3.78(m, 1H), 3.87(m, 2H), 4.02-4.04(m, 1H), 4.13(m, 1H), 4.30(m, 1H) , 4.41 (m, 1H), 5.31-5.34 (m, 2H), 9.16 (s, 1H) C26H35N9O5S HPLC 98.4% wt (M+1) 586.2 542

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3a-(hydroxymethyl )octahydro-1H-pyrrolo[3,4-c]pyridine-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en- 2-carboxylic acid ¹ H NMR (D ₂ O) -1.08 (d, 3H), 1.20 (d, 3H), 1.64-1.80 (m, 1H), 1.97-1.99 (m, 2H), 2.37-2.44(m, 2H), 2.73(m, 2H), 3.04-3.09(m, 1H), 3.13-3.22(m, 2H) , 3.34 (m, 3H), 3.49 (m, 3H), 3.61 (m, 3H), 3.78-3.81 (m, 1H), 4.00-4.02 (m , 1H), 4.18 (m, 1H), 4.30-4.34 (m, 1H), 5.31-5.35 (m, 2H), 9.24 (s, 1H) C26H37N9O6S HPLC 97 .4% mass (M+1) 604.1 543

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(5-aminooctahydrocyclopenta[ c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.08 (d, 3H), 1.22 (d, 3H), 1.33-1.38 (m, 2H), 1.70-1.73 (m, 2H), 2.33-2.34 (m, 2H), 2.69-2.77 (m, 3H), 3.18-3.23 (m, 2H), 3.34-3.36 ( m, 2H), 3.40-3.46 (m, 2H), 3.50-3.56 (m, 2H), 3.63-3.67 (m, 1H), 3.83 (m, 1H), 4.01-4.03 (m, 1H), 4.29-4.31 (m, 1H), 5.30-5.31 (m, 2H), 9.15 (s, 1H) C25H35N9O5S HPLC 90.3 wt% (M+1) 574.3 544

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3R,4R )-3-guanidino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.23 (d, 3H), 1.92 (m, 1H), 2.93-2.97 (m, 2H), 3 .21-3.22 (m, 2H), 3.35-3.37 (m, 1H), 3.49-3.54 (m, 2H), 3.64-3.73 (m, 2H) , 3.83-3.97 (m, 2H), 4.04-4.05 (m, 2H), 4.29-4.37 (m, 2H), 5.29-5.31 (m, 2H), 9.16 (s, 1H) C23H33N11O6S HPLC 98.2 wt% (M+1) 592.2 545

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3R,4S )-3-guanidino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.10 (d, 3H), 1.24 (d, 3H), 1.93 (m, 1H), 2.95-2.99 (m, 2H), 3 .24-3.26 (m, 2H), 3.37-3.39 (m, 1H), 3.51-3.56 (m, 2H), 3.66-3.75 (m, 2H) , 3.85-3.99 (m, 2H), 4.06-4.07 (m, 2H), 4.31-4.39 (m, 2H), 5.31-5.33 (m, 2H), 9.18 (s, 1H) C23H33N11O6S HPLC 98.2% wt (M+1) 592.2 546

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)
ethyl)-3-((3S,5S)-5-((3S,4R)-3-guanidino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1- azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.08 (d, 3H), 1.21 (d, 3H), 1.88-1.89 (m, 1H), 2.91-2.95 (m, 2H), 3.19-3.21(m, 2H), 3.33-3.35(m, 1H), 3.47-3.52(m, 2H), 3.62-3.71( m, 2H), 3.81-3.95 (m, 2H), 4.02-4.03 (m, 2H), 4.27-4.35 (m, 2H), 5.27-5, 29 (m, 2H), 9.14 (s, 1H) C23H33N11O6S HPLC 92.6 wt% (M+1) 592.2 547

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3aS,5R ,6S)-5-amino-6-hydroxy-3a-(hydroxymethyl)octahydro-cyclopenta[c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo-[3 ,2,0]-hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.21 (d, 3H), 1.80 (m, 1H), 1.86-1.96 (m, 2H), 2 .08 (m, 2H), 2.48-2.54 (m, 2H), 2.87-2.93 (m, 2H), 3.21-3.28 (m, 3H), 3.38 (m, 2H), 3.47 (m, 1H), 3.52-3.57 (m, 1H), 3.82-3.88 (m, 1H), 4.01-4.03 (m , 1H), 4.08 (m, 1H), 4.28-4.29 (m, 1H), 4.31 (m, 1H), 5.30-5.31 (m, 2H), 9, 15 (s, 1H) C26H37N9O7S HPLC 90.9 wt% (M+1) 620.6 548

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,3R ,4R)-3-amino-4-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept- 2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.23 (d, 3H), 1.89-1.93 (m, 1H), 2.93-2.96 (m, 1H), 3.21-3.25(m, 1H), 3.31-3.34(m, 2H), 3.47-3.48(m, 2H), 3.51(m, 2H) , 3.57-3.59 (m, 1H), 3.61-3.69 (m, 1H), 3.73-3.88 (m, 2H), 4.03-4.08 (m, 2H), 4.29 (m, 1H), 4.32-4.39 (m, 1H), 5.31 (m, 2H), 9.16 (s, 1H) C23H33N9O7S HPLC 97.9% wt ( M+1) 580.4 549

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2R,3R ,4S)-4-amino-3-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept- 2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.21 (d, 3H), 1.88-1.92 (m, 1H), 2.95-2.98 (m, 1H), 3.23-3.27(m, 1H), 3.33-3.36(m, 2H), 3.49-3.50(m, 2H), 3.53(m, 2H) , 3.59-3.61 (m, 1H), 3.63-3.71 (m, 1H), 3.75-3.90 (m, 2H), 4.05-4.10 (m, 2H), 4.31 (m, 1H), 4.34-4.41 (m, 1H), 5.33 (m, 2H), 9.17 (s, 1H) C23H33N9O7S HPLC 99% wt (M+ 1) 580.4 550

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3aR,6aR )-3a-(hydroxymethyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2- en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.24 (d, 3H), 1.81 (m, 1H), 2.19 (m, 1H), 2.43 (m , 1H), 2.76-2.80 (m, 2H), 3.24-3.28 (m, 1H), 3.44-3.46 (m, 3H), 3.55-3.64 (m, 3H), 3.84 (m, 2H), 4.01-4.03 (m, 1H), 4.28-4.32 (m, 2H), 5.31-5.32 (m , 2H), 9.16 (s, 1H) C22H32N10O4S
HPLC 94.7% wt (M+1) 533.2 551

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(-2-( hydroxymethyl)octahydropyrrolo[3,4-b]pyrrole-5-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.24 (d, 3H), 1.99-2.03 (m, 3H), 2.86-2.87 (m, 3H), 3.25-3.35(m, 4H), 3.46-3.48(m, 3H), 3.61-3.64(m, 2H), 3.74-3.87( m, 3H), 4.03-4.05 (m, 1H), 4.29-4.32 (m, 1H), 4.40-4.42 (m, 1H), 5.31-5, 32 (m, 2H), 9.16 (s, 1H) C25H35N9O6S HPLC 97% wt (M+1) 590.1 552

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,3aS ,6aS)-2-(hydroxymethyl)octahydropyrrolo[3,4-b]pyrrole-5-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept- 2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.10 (d, 3H), 1.25 (d, 3H), 2.01-2.05 (m, 3H), 2.88-2.89 (m, 3H), 3.27-3.37(m, 4H), 3.48-3.50(m, 3H), 3.63-3.66(m, 2H), 3.76-3.89( m, 3H), 4.05-4.07 (m, 1H), 4.31-4.34 (m, 1H), 4.42-4.44 (m, 1H), 5.33-5, 34 (m, 2H), 9.17 (s, 1H) C25H35N9O6S HPLC 93.2% wt (M+1) 590.1 553

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3R,4R )-4-amino-3-hydroxypiperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.24 (d, 3H), 1.50-1.56 (m, 1H), 1.75-1.78 (m, 2H), 2.03-2.06(m, 1H), 2.81-2.87(m, 2H), 2.96-2.99(m, 1H), 3.15-3.23( m, 3H), 3.41-3.48 (m, 2H), 3.74 (m, 2H), 3.87 (m, 1H), 4.02-4.05 (m, 1H), 4 .29 (m, 1H), 4.31-4.32 (m, 1H), 5.31-5.32 (m, 2H), 9.16 (s, 1H) C23H33N9O6S HPLC 98.4% wt ( M+1) 564.1 554

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4S )-4-amino-3-hydroxypiperidine-1-carbonyl)-pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.25 (d, 3H), 1.52-1.58 (m, 1H), 1.77-1.80 (m, 2H), 2.05-2.08 (m, 1H), 2.83-2.89 (m, 2H), 2.98-3.01 (m, 1H), 3.17-3.25 ( m, 3H), 3.43-3.50 (m, 2H), 3.76 (m, 2H), 3.89 (m, 1H), 4.04-4.07 (m, 1H), 4 .31 (m, 1H), 4.33-4.34 (m, 1H), 5.33-5.34 (m, 2H), 9.18 (s, 1H) C23H33N9O6S HPLC 98.4% wt ( M+1) 564.1 555

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(6a-(hydroxymethyl )octahydropyrrolo[3,4-b]pyrrole-5-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.24 (d, 3H), 1.82-1.90 (m, 5H), 2.30-2.33 (m, 1H), 2.88-2.91 (m, 2H), 3.22-3.38 (m, 2H), 3.41-3.49 (m, 3H), 3.58-3.65 ( m, 2H), 3.78-3.79 (m, 3H), 3.92-3.98 (m, 2H), 4.04-4.06 (m, 1H), 5.32-5, 3 (d, 2H), 9.17 (s, 1H) C25H35N9O6S HPLC 97.5 wt% (M+1) 590.2 556

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(6a-(hydroxymethyl )octahydropyrrolo[3,4-b]pyrrole-5-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.3 (d, 3H), 1.88-1.96 (m, 5H), 2.34-2.37 (m, 1H), 2.92-2.95 (m, 2H), 3.26-3.42 (m, 2H), 3.44-3.53 (m, 3H), 3.62-3.69 ( m, 2H), 3.82-3.83 (m, 3H), 4.01-4.07 (m, 2H), 4.12-4.14 (m, 1H), 5.38-5, 36(d, 2H), 9.25(s, 1H) C25H35N9O6S HPLC 97.9% wt (M+1) 590.6 557

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(5-oxa-2-azaspiro[3.4]octane -7-ylthio)-4-methyl-7-oxo-1-azabicyclo-[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.23 (d, 3H), 1.89 (m, 1H), 2.22-2.26 (m, 1H), 2 .56-2.62 (m, 1H), 3.15-3.18 (m, 1H), 3.45-3.47 (m, 1H), 3.77-3.84 (m, 2H) , 4.01-4.03 (m, 1H), 4.08-4.09 (m, 1H), 4.17-4.32 (m, 2H), 4.17-4.32 (m, 2H), 5.26-5.36 (d, 2H), 9.16 (s, 1H) C19H25N7O5S HPLC 90.3% wt (M+1) 464.1 558

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(5-oxa-2-azaspiro[3.4]octane -7-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.11 (d, 3H), 1.25 (d, 3H), 1.91 (m, 1H), 2.24-2.28 (m, 1H), 2 .58-2.64 (m, 1H), 3.17-3.20 (m, 1H), 3.47-3.49 (m, 1H), 3.79-3.86 (m, 2H) , 4.03-4.05 (m, 1H), 4.10-4.11 (m, 1H), 4.19-4.34 (m, 2H), 4.19-4.34 (m, 2H), 5.28-5.38 (d, 2H), 9.18 (s, 1H) C19H25N7O5S HPLC 90% wt (M+1) 464.1 559

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(5-carbamimidoyloctahydro- 1H-pyrrolo[3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.19 (d, 3H), 1.21 (d, 3H), 1.68-1.69 (m, 1H), 1.83-1.87 (m, 3H), 2.02-2.09 (m, 4H), 2.48-2.52 (m, 1H), 2.89-2.90 (m, 1H), 3.01-3.17 ( m, 2H), 3.20-3.29 (m, 1H), 3.44-3.70 (m, 3H), 3.71-3.90 (m, 1H), 4.00-4, 02 (m, 1H), 4.21-4.30 (m, 3H), 4.47-4.70 (m, 1H), 5.29-5.33 (m, 2H), 9.14 ( s, 1H) C26H37N11O5S HPLC 98.7% wt (M+1) 616.2 560

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(5-carbamimidoyloctahydro- 1H-pyrrolo[3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.20 (d, 3H), 1.23 (d, 3H), 1.72-1.73 (m, 1H), 1.87-1.71 (m, 3H), 2.06-2.13(m, 4H), 2.52-2.56(m, 1H), 2.93-2.94(m, 1H), 3.05-3.21( m, 2H), 3.24-3.33 (m, 1H), 3.48-3.74 (m, 3H), 3.76-3.95 (m, 1H), 4.04-4, 06 (m, 1H), 4.25-4.34 (m, 3H), 4.51-4.74 (m, 1H), 5.33-5.37 (m, 2H), 9.15 ( s, 1H) C26H37N11O5S HPLC 98.7% wt (M+1) 616.2 561

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(6a-(hydroxymethyl )octahydropyrrolo[3,4-b]-pyrrole-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.21 (d, 3H), 1.69-1.81 (m, 3H), 2.19-2.20 (m, 1H), 2.81-2.82 (m, 1H), 2.99-3.01 (m, 1H), 3.09-3.22 (m, 3H), 3.37-3.52 ( m, 4H), 3.62-3.66 (m, 4H), 3.81-3.82 (m, 1H), 3.93-3.96 (m, 2H), 4.28-4, 29 (m, 1H), 5.30-5.31 (d, 2H), 9.14 (s, 1H) C25H35N9O6S HPLC 90.4% wt (M+1) 590.4 562

5-((2S,4S)-4-((4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-2-carboxy- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl-thio)pyrrolidin-2-carbonyl)octahydro-1H-pyrrolo[3,4-c]pyridine- 3a-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.21 (d, 3H), 1.37-1.38 (m, 1H), 1.60-1.61 (m, 1H), 1.81-2.09 (m, 4H), 3.11-3.35 (m, 4H), 3.44-3.47 (m, 2H), 3.52-3.57 ( m, 3H), 3.60-3.66 (m, 2H), 3.84-3.88 (m, 1H), 3.91-4.03 (m, 1H), 4.87-5, 29 (m, 2H), 5.30-5.46 (m, 2H), 9.14 (s, 1H) C26H35N9O7S HPLC 94.7 wt% (M+1) 618.3 563

5-((2S,4S)-4-((4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-2-carboxy- 4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl-thio)pyrrolidin-2-carbonyl)octahydro-1H-pyrrolo[3,4-c]pyridine- 3a-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.23 (d, 3H), 1.41-1.42 (m, 1H), 1.64-1.65 (m, 1H), 1.85-2.13(m, 4H), 3.15-3.39(m, 4H), 3.48-3.51(m, 2H), 3.56-3.61( m, 3H), 3.64-3.70 (m, 2H), 3.88-3.92 (m, 1H), 3.95-4.07 (m, 1H), 4.91-5, 33 (m, 2H), 5.34-5.50 (m, 2H), 9.15 (s, 1H) C26H35N9O7S HPLC 94.7%
Mass (M+1) 618.3 564

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((1S, 7R )-3,8-Diaza-tricyclo[5.2.1.01.5]decan-3-carbonyl)-pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2, 0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.21 (d, 3H), 1.71-1.79 (m, 3H), 1.85-2.05 (m, 2H), 2.33-2.45(m, 1H), 2.82-2.84(m, 1H), 2.98-3.01(m, 1H), 3.12-3.27( m, 3H), 3.38-3.44 (m, 2H), 3.61-3.66 (m, 1H), 3.73-3.75 (m, 2H), 3.81-3, 89 (m, 1H), 4.00-4.02 (m, 1H), 4.10-4.20 (m, 2H), 4.30-4.47 (m, 2H), 5.25- 5.34 (d, 2H), 9.13 (s, 1H) C26H35N9O5S HPLC 97.9 wt% (M+1) 586.3 565

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4R )-3-amino-4-guanidinopyrrolidine-1-carbonyl)-pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.24 (d, 3H), 1.81-1.89 (m, 2H), 2.86-2.88 (m, 1H), 3.24-3.30(m, 2H), 3.36-3.48(m, 3H), 3.55-3.68(m, 3H), 3.70-3.75( m, 1H), 3.80-3.89 (m, 1H), 4.03-4.05 (m, 1H), 4.15-4.70 (m, 2H), 5.27-5, 36 (d, 2H), 9.16 (s, 1H) C23H34N12O5S HPLC 96.9 wt% (M+1) 591.2 566

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-guanidinoazetidine- 1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.22 (d, 3H), 1.79-1.88 (m, 2H), 2.70-2.72 (m, 1H), 3.12-3.20 (m, 2H), 3.30-3.46 (m, 2H), 3.80-3.92 (m, 2H), 4.00-4.02 ( m, 1H), 4.13-4.29 (m, 2H), 4.42-4.54 (m, 3H), 5.30-5.35 (d, 2H), 9.15 (s, 1H) C22H31N11O5S HPLC 97.2 wt% (M+1) 562.3 567

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((R)- 3-(2-guanidinoacetamido)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.21 (d, 3H), 1.78-1.87 (m, 3H), 1.96-1.98 (m, 1H), 2.09-2.16(m, 2H), 2.81-2.83(m, 1H), 3.19-3.25(m, 2H), 3.46-3.48( m, 3H), 3.60-3.63 (m, 1H), 3.83-3.87 (m, 3H), 4.01-4.02 (m, 1H), 4.21-4, 32 (m, 2H), 5.24-5.33 (d, 2H), 9.14 (s, 1H) C25H36N12O6S HPLC 98.1% wt (M+1) 633.1 568

(4R,5S,6R)-3-((3S,5S)-5-((R)-3-aminopyrrolidine-1-carbonyl)pyrrolidine-3-ylthio)-6-((R)-1-(2 -(azetidin-3-yl)acetamido)ethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.22 (d, 3H), 1.73-1.78 (m, 1H), 1.88-2.20 (m, 2H), 2.41-2.44(m, 2H), 2.54-2.66(m, 3H), 2.79-2.82(m, 2H), 3.11-3.14( m, 1H), 3.26-3.37 (m, 3H), 3.53-3.68 (m, 2H), 3.70-3.74 (m, 3H), 3.81-3, 84 (m, 3H), 3.90-3.95 (m, 1H), 3.97-4.04 (m, 1H), C24H36N6O5S HPLC 94.3% wt (M+1) 521.2 569

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(1-Carbamimidoyloctahydro- pyrrolo[3,4-b]-pyrrole-5-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.06 (d, 3H), 1.20 (d, 3H), 1.78-1.79 (m, 1H), 1.86-1.87 (m, 2H), 2.87-2.89 (m, 1H), 3.19-3.27 (m, 4H), 3.43-3.49 (m, 4H), 3.59-3.65 ( m, 1H), 3.72-3.77 (m, 2H), 3.87-3.88 (m, 1H), 3.99-4.01 (m, 1H), 4.25-4, 29 (m, 1H), 4.37-4.43 (m, 2H), 5.28-5.32 (d, 2H), 9.13 (s, 1H) C25H35N11O5S HPLC 91.1% wt (M +1) 602.1 570

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(1-carbamimidoyl- octahydropyrrolo[3,4-b]-pyrrole-5-carbonyl)pyrrolidin-3-yl-thio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.08 (d, 3H), 1.22 (d, 3H), 1.82-1.83 (m, 1H), 1.90-1.91 (m, 2H), 2.91-2.93(m, 1H), 3.23-3.31(m, 4H), 3.47-3.53(m, 4H), 3.63-3.69( m, 1H), 3.76-3.81 (m, 2H), 3.91-3.92 (m, 1H), 4.03-4.05 (m, 1H), 4.29-4, 33 (m, 1H), 4.41-4.47 (m, 2H), 5.32-5.36 (d, 2H), 9.13 (s, 1H) C25H35N11O5S HPLC 96.9% wt (M +1) 602.1 571

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((1R, 7R )-3,8-Diaza-tricyclo[5.2.1.01.5]decan-8-carbonyl)-pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2, 0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.21 (d, 3H), 1.67-1.79 (m, 4H), 1.93-1.98 (m, 1H), 2.39-2.40(m, 1H), 2.77-2.78(m, 1H), 2.89-2.95(m, 1H), 3.14-3.15( m, 1H), 3.22-3.23 (m, 1H), 3.29-3.37 (m, 3H), 3.43-3.45 (m, 2H), 3.51-3, 57 (m, 1H), 3.60-3.67 (m, 1H), 3.80-3.81 (m, 1H), 4.00-4.02 (m, 1H), 4.14- 4.17 (m, 1H), 4.27-4.33 (m, 2H), 5.25-5.34 (m, 2H), 9.14 (s, 1H) C26H35N9O5S HPLC 97.9% wt (M+1) 586.2 572

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(3 -amino-2-hydroxypropylcarbamoyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.15 (d, 3H), 1.22 (d, 3H), 1.45-1.52 (m, 2H), 1.67-1.69 (m, 1H), 1.78-1.87 (m, 3H), 2.52-2.53 (m, 1H), 2.74-2.80 (m, 3H), 2.99-3.02 ( m, 1H), 3.02-3.22 (m, 3H), 3.35-3.36 (m, 1H), 3.38-3.44 (m, 1H), 3.60-3, 64 (m, 1H), 3.74-3.77 (m, 1H), 3.84-3.85 (m, 2H), 4.00-4.02 (m, 1H), 4.21- 4.70 (m, 3H), 5.25-5.34 (m, 2H), 9.13 (s, 1H) C27H40N10O7S HPLC 96.5% wt (M+1) 649.2 573

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(4-(3 -amino-2-hydroxypropylcarbamoyl)piperidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.24 (d, 3H), 1.48-1.55 (m, 2H), 1.70-1.72 (m, 1H), 1.81-1.90 (m, 3H), 2.55-2.56 (m, 1H), 2.77-2.83 (m, 3H), 3.02-3.05 ( m, 1H), 3.05-3.25 (m, 3H), 3.38-3.39 (m, 1H), 3.41-3.47 (m, 1H), 3.63-3, 67 (m, 1H), 3.77-3.81 (m, 1H), 3.87-3.88 (m, 2H), 4.03-4.05 (m, 1H), 4.24- 4.73 (m, 3H), 5.28-5.37 (m, 2H), 9.15 (s, 1H) C27H40N10O7S HPLC 97.9% wt (M+1) 648.73 574

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3aS,5S ,6aR)-3a,5-diaminooctahydrocyclopenta[c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.21 (d, 3H), 1.64-1.69 (m, 2H), 1.70-1.78 (m, 2H), 1.84-1.95(m, 1H), 2.09-2.10(m, 1H), 2.33-2.35(m, 1H), 2.42-2.46( m, 1H), 2.76-2.77 (m, 1H), 3.08-3.09 (m, 1H), 3.18-3.19 (m, 1H), 3.20-3, 22 (m, 2H), 3.27-3.30 (m, 1H), 3.43-3.46 (m, 1H), 3.44-3.50 (m, 2H), 3.60- 3.66 (m, 1H), 3.91-3.99 (m, 2H), 5.27-5.29 (m, 2H), 9.14 (s, 1H) C25H36N10O5S HPLC 91.8% wt (M+1) 589.1 575

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(((R) -3-aminopyrrolidin-1-yl) (imino)-methylcarbamoyl)-pyrrolidin-3-yl-thio)-4-methyl-7-oxo-1-azabicyclo-[3.2.0]-hept-2-ene -2-carboxylic acid ¹ H NMR (D ₂ O) -1.05 (d, 3H), 1.20 (d, 3H), 1.73 (m, 1H), 1.94 (m, 2H), 2.04 (m , 1H), 2.32 (m, 2H), 2.49 (m, 1H), 3.24 (m, 2H), 3.44-3.55 (m, 3H), 3.59 (m, 1H), 3.82 (m, 1H), 4.01-4.03 (m, 1H), 4.19-4.28 (m, 1H), 4.34 (m, 1H), 5.28 -5.29 (d, 2H), 9.13 (s, 1H) C23H33N11O5S HPLC 97.1% wt (M+1) 576.4 576

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((2S,4S )-4-guanidino-2-(hydroxymethyl)-pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid ¹ H NMR (D ₂ O) -1.03 (d, 3H), 1.17 (d, 3H), 1.80-1.83 (m, 2H), 2.36-2.43 (m, 1H), 2.74-2.82 (m, 1H), 3.14-3.18 (m, 2H), 3.24-3.26 (m, 1H), 3.41-3.45 ( m, 2H), 3.52-3.58 (m, 1H), 3.75-3.79 (m, 2H), 3.80-3.87 (m, 1H), 3.96-3, 98 (m, 1H), 4.03-4.08 (m, 2H), 4.22-4.26 (m, 1H), 4.33-4.35 (m, 1H), 5.25- 5.30 (d, 2H), 9.10 (s, 1H) C24H35N11O6S HPLC 99.1% wt (M+1) 606.1 577

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(1-(2 -aminoethyl)octahydropyrrolo[3,4-b]pyrrole-5-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.21 (d, 3H), 1.51 (m, 1H), 1.86 (m, 1H), 2.27 (m , 1H), 2.74-2.90 (m, 3H), 3.01-3.14 (m, 3H), 3.22 (m, 4H), 3.34-3.55 (m, 4H ), 3.68 (m, 2H), 3.72 (m, 1H), 3.84 (m, 1H), 3.99-4.02 (m, 1H), 4.28-4.30 ( m, 2H), 5.29 (d, 2H), 9.14 (s, 1H) C26H38N10O5S HPLC 97.9 wt% (M+1) 603.4 578

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(1-(2 -aminoethyl) octahydropyrrolo[3,4-b]pyrrole-5-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.23 (d, 3H), 1.53 (m, 1H), 1.88 (m, 1H), 2.29 (m , 1H), 2.76-2.92 (m, 3H), 3.03-3.16 (m, 3H), 3.24 (m, 4H), 3.36-3.57 (m, 4H ), 3.70 (m, 2H), 3.74 (m, 1H), 3.86 (m, 1H), 4.01-4.04 (m, 1H), 4.30-4.32 ( m, 2H), 5.31 (d, 2H), 9.16 (s, 1H) C26H38N10O5S HPLC 91.6 wt% (M+1) 603.4 579

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(2-guanidinoethylthio)-4-methyl-7-oxo- 1-azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid ¹ H NMR (D ₂ O) -0.93 (d, 3H), 1.21 (d, 3H), 1.86 (m, 1H), 2.70-2.77 (m, 1H), 2 .97-3.03 (m, 1H), 3.23-3.28 (m, 1H), 3.30-3.36 (m, 1H), 3.40-3.42 (m, 1H) , 3.95-3.98 (m, 1H), 4.26-4.31 (m, 1H), 5.31-5.33 (m, 2H), 9.14 (s, 1H) C16H23N9O4S HPLC 94.4% mass (M+1) 438.2 580

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3aR,6aS )-2-iminooctahydropyrrolo[3,4-d]imidazole-5-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2 -carboxylic acid ¹ H NMR (D ₂ O) -1.05 (d, 3H), 1.31 (d, 3H), 1.71-1.79 (m, 1H), 1.88-1.97 (m, 1H), 2.14-2.43(m, 1H), 2.89-3.01(m, 1H), 3.20-3.36(m, 2H), 3.42-3.49( m, 1H), 3.53-3.55 (m, 2H), 3.61-3.68 (m, 1H), 3.76-3.79 (m, 1H), 3.82-3, 85 (m, 2H), 3.85-3.86 (m, 1H), 3.99-4.03 (m, 1H), 4.09-4.11 (m, 1H), 5.34- 5.43 (m, 2H), 9.26 (s, 1H) C23H31N11O5S HPLC 90.3 wt% (M+1) 574.1 581

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(5-guanidinooctahydrocyclopenta[ c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.08 (d, 3H), 1.22 (d, 3H), 1.51-1.52 (m, 1H), 1.61-1.62 (m, 1H), 1.69-1.70 (m, 1H), 1.81-1.82 (m, 1H), 2.20-2.30 (m, 1H), 2.62-2.69 ( m, 2H), 2.89-2.90 (m, 1H), 2.91-2.96 (m, 1H), 3.06-3.08 (m, 1H), 3.10-3, 11(m, 1H), 3.23-3.24(m, 1H) 3.33-3.36(m, 1H), 3.43-3.47(m, 2H), 3.52-3 .58 (m, 2H), 3.62-3.69 (m, 1H), 3.80-3.82 (m, 1H), 3.90-4.03 (m, 1H), 4.29 -4.47 (m, 1H), 5.30-5.33 (d, 2H), 9.15 (s, 1H) C26H37N11O5S HPLC 93.8 wt% (M+1) 616.2 582

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)-ethyl)-3-((3S,5S)-5-((S) -3-guanidino-pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.09 (d, 3H), 1.22 (d, 3H), 2.23-2.27 (m, 2H), 2.86-2.92 (m, 1H), 3.21-3.22(m, 1H), 3.26-3.29(m, 1H), 3.30-3.39(m, 1H), 3.45-3.46( m, 2H), 3.50-3.58 (m, 3H), 3.60-3.67 (m, 1H), 3.74-3.78 (m, 1H), 3.78-3, 88 (m, 1H), 3.90-4.03 (m, 1H), 4.13-4.18 (m, 1H), 4.27-4.30 (m, 1H), 5.30- 5.34 (d, 2H), 9.15 (s, 1H) C23H33N11O5S HPLC 97.5 wt% (M+1) 576.1 583

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4R )-3-guanidino-4-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 1.82-1.83 (m, 1H), 1.97-1.98 (m, 1H), 2.50-2.57 (m, 1H), 2.88-2.89 (m, 1H), 3.23-3.32 (m, 2H), 3.32-3.38 ( m, 2H), 3.41-3.44 (m, 1H), 3.54-3.55 (m, 1H), 3.67-3.78 (m, 2H), 3.90-3, 92 (m, 2H), 4.03-4.07 (m, 2H), 4.32-4.38 (m, 2H), 5.35-5.44 (m, 2H), 9.24 ( s, 1H) C24H35N11O6S HPLC 94.5 wt% (M+1) 606.3 584

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3S,4R )-3-amino-4-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 1.89-1.97 (m, 2H), 2.61-2.71 (m, 1H), 2.99-3.00 (m, 2H), 3.28-3.43 (m, 2H), 3.44-3.46 (m, 1H), 3.54-3.67 ( m, 4H), 3.70-3.78 (m, 3H), 3.81-3.88 (m, 1H), 3.91-3.96 (m, 1H), 3.99-4, 06 (m, 1H), 5.34-5.43 (d, 2H), 9.25 (s, 1H) C23H33N9O6S HPLC 94% wt (M+1) 564.4 585

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3aR,5R )-5-guanidino-3a-(hydroxymethyl)octahydrocyclopenta[c]pyrrole-2-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2- en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.22 (d, 3H), 1.31 (d, 3H), 1.37-1.38 (m, 1H), 1.50-1.54 (m, 1H), 1.97-1.98 (m, 4H), 2.19-2.20 (m, 1H), 2.74-2.89 (m, 2H), 3.22-3.38 ( m, 3H), 3.470-3.49 (m, 4H), 3.55-4.12 (m, 5H), 4.61 (m, 1H), 5.38-5.54 (d, 2H) , 9.25 (s, 1H) C27H39N11O6S HPLC 95.8 wt% (M+1) 646.1 586

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 4-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.31 (d, 3H), 1.82-1.96 (m, 1H), 2.74-2.95 (m, 2H), 3.27-3.33(m, 2H), 3.41-3.44(m, 3H), 3.51-3.53(m, 2H), 3.66-3.77( m, 4H), 3.83-3.86 (m, 2H), 4.38-4.80 (m, 2H), 5.34-5.43 (d, 2H), 9.23 (s, 1H) C23H33N9O6S
HPLC 94.5% mass (M+1) 564.3 587

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3-amino- 4-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.18 (d, 3H), 1.33 (d, 3H), 1.84-1.98 (m, 1H), 2.76-2.97 (m, 2H), 3.29-3.35(m, 2H), 3.43-3.46(m, 3H), 3.53-3.55(m, 2H), 3.68-3.79( m, 4H), 3.85-3.88 (m, 2H), 4.40-4.82 (m, 2H), 5.36-5.45 (d, 2H), 9.25 (s, 1H) C23H33N9O6S
HPLC 98.2% mass (M+1) 564.3 588

(4R,5S,6R)-3-((3S,5S)-5-((3R,4R)-3-guanidino-4-hydroxypyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-6 -((R)-1-(2-(methylamino)acetamido)ethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.07 (d, 3H), 1.15 (d, 3H), 1.79-1.86 (m, 1H), 2.63 (s, 3H), 3 .24-3.25 (m, 2H), 3.25-3.47 (m, 4H), 3.49-3.51 (m, 1H), 3.53-3.55 (m, 2H) , 3.75-3.76 (m, 2H), 3.80-3.87 (m, 2H), 4.00-4.03 (m, 2H), 4.31-4.39 (m, 2H) C23H36N8O6S
HPLC 95.6% mass (M+1) 553.2 589

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(guanidinomethyl)pyrrolidine- 3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.28 (d, 3H), 1.34 (d, 3H), 1.97-1.99 (m, 1H), 2.99 (m, 1H), 3 .00 (m, 2H), 3.04 (m, 1H), 3.31-3.36 (m, 1H), 3.44-3.48 (m, 1H), 3.57-3.60 (m, 1H), 3.73-3.77 (m, 1H), 4.05 (m, 1H), 4.13-3.16 (m, 1H), 4.40-4.43 (m , 1H), 5.42 (d, 2H), 9.27 (s, 1H) C19H28N10O4S
HPLC 89.8 wt% (M+1) 493.2 590

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3,6- diazabicyclo[3.2.0]heptan-3-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.26 (d, 3H), 1.31 (d, 3H), 1.79-1.97 (m, 2H), 2.84-2.85 (m, 1H), 3.20-3.22(m, 1H), 3.33-3.41(m, 1H), 3.48-3.53(m, 1H), 3.73-3.74( m, 2H), 3.90-3.91 (m, 1H), 3.97-3.98 (m, 2H), 3.99-4.00 (m, 1H), 4.10-4, 12 (m, 1H), 4.18-4.26 (m, 2H), 4.36-4.46 (m, 2H), 5.03-5.10 (m, 1H), 5.30- 5.44 (s, 2H), 9.25 (s, 1H) C23H31N9O5S HPLC 96.1% wt (M+1) 546.2 591

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(3,6- diazabicyclo[3.2.0]heptan-3-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.28(d, 3H), 1.33 (d, 3H), 1.81-1.99 (m, 2H), 2.86-2.87 (m, 1H), 3.22-3.24(m, 1H), 3.35-3.43(m, 1H), 3.50-3.55(m, 1H), 3.75-3.76( m, 2H), 3.92-3.93 (m, 1H), 3.99-4.00 (m, 2H), 4.01-4.02 (m, 1H), 4.12-4, 14 (m, 1H), 4.20-4.28 (m, 2H), 4.38-4.48 (m, 2H), 5.05-5.12 (m, 1H), 5.32- 5.46 (d, 2H), 9.25 (s, 1H) C23H31N9O5S HPLC 96.1% wt (M+1) 546.2 592

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-((3R,4S )-3-guanidino-4-(hydroxymethyl)pyrrolidine-1-carbonyl)pyrrolidin-3-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2- carboxylic acid ¹ H NMR (D ₂ O) -1.17 (d, 3H), 1.32 (d, 3H), 1.83-1.97 (m, 1H), 2.75-2.96 (m, 2H), 3.28-3.34 (m, 2H), 3.42-3.45 (m, 3H), 3.52-3.54 (m, 2H), 3.67-3.78 ( m, 4H), 3.84-3.87 (m, 2H), 4.39-4.81 (m, 2H), 5.35-5.44 (d, 2H), 9.24 (s, 1H) C24H35N11O6S 27 HPLC 90% mass (M+1) 606.2 593

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3-(1-((R )-pyrrolidin-3-ylmethyl)-1H-pyrazol-4-ylthio)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -0.97 (d, 3H), 1.29 (d, 3H), 1.78-1.80 (m, 1H), 1.94-1.98 (m, 2H), 2.14-2.22(m, 1H), 2.86-2.96(m, 2H), 3.05-3.10(m, 1H), 3.34-3.44( m, 2H), 3.96-3.99 (m, 1H), 4.31-4.33 (m, 3H), 5.36-5.40 (m, 2H), 7.70-7, 73 (m, 1H), 7.93-7.97 (m, 1H), 9.23 (s, 1H) C21H27N9O4S HPLC 91.35 wt% (M+1) 502.3 594

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(1-((1-(2-aminoethyl)-1 -methylpiperidinium-4-yl)methyl)-1H-pyrazol-4-ylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate ¹ H NMR (D ₂ O) -1.13 (d, 3H), 1.28 (d, 3H), 2.20-2.29 (m, 3H), 2.97 (m, 2H), 3 .87-3.88 (m, 2H), 3.47-3.48 (m, 3H), 3.87-3.88 (m, 3H), 3.99-4.15 (m, 2H) , 4.30 (m, 2H), 5.36 (d, 2H), 7.43-7.44 (m, 2H), 7.54-7.56 (m, 2H), 7.93 (s , 1H), 8.04 (s, 1H), 9.22 (s, 1H) C25H36N10O4S HPLC 91.4 wt% (M+1) 573.1 595

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(4-(1-(3-aminopropyl)-1H- pyrazol-4-yl)benzylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -0.86-0.88 (d, 3H), 1.68 (d, 3H), 2.18-2.19 (m, 2H), 3.02-3, 06 (m, 2H), 3.31-3.32 (m, 2H), 3.47-3.48 (m, 2H), 3.86-3.87 (m, 1H), 4.11- 4.13(m, 2H), 4.23-4.24(m, 1H), 5.27-5.28(m, 2H), 7.63(m, 2H), 7.84(m, 2H), 8.39 (s, 1H), 8.43 (s, 1H) 9.14 (s, 1H) C26H31N9O4S HPLC 94.4 wt% (M+1) 566.2 596

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(4-(1-(3-aminopropyl)-2- methyl-1H-pyrazol-2-y-4-yl)benzylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate ¹ H NMR (D ₂ O) -1.00 (d, 3H), 1.18 (d, 3H), 2.22-2.23 (d, 2H), 3.00-3.01 (m, 2H), 3.31-3.33(m, 1H), 3.69-3.71(m, 2H), 3.91-3.92(m, 1H), 3.99-4.01( m, 1H), 4.07 (s, 3H), 4.20-4.21 (m, 1H), 4.47-4.49 (m, 1H), 5.25-5.26 (m, 2H), 7.35-7.37(m, 2H), 7.43-7.47(m, 2H), 8.44(s, 1H), 8.50(s, 1H), 9.12 (s, 1H) C27H33N9O4S HPLC 96.7% (M+1) 580.2 597

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-3-(2-methyl-1-((R )-pyrrolidin-3-ylmethyl)-1H-pyrazol-2-y-4-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate ¹ H NMR (D ₂ O) -0.89-0.91 (d, 3H), 1.20 (d, 3H), 1.79-1.80 (m, 1H), 2.15-2, 16 (m, 1H), 2.76-2.77 (m, 1H), 2.99-3.06 (m, 2H), 3.41-3.42 (m, 2H), 3.50- 3.51 (m, 1H), 3.92-3.94 (m, 1H), 3.99-4.00 (m, 1H), 4.05 (s, 3H), 4.10-4, 11 (m, 1H), 4.44-4.45 (m, 1H), 5.24-5.25 (m, 2H), 8.45 (s, 1H), 8.55 (s, 1H) , 9.13 (s, 1H) C22H29N9O4S
HPLC 90% (M+1) 516.2 598

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(4-(1-(3-aminopropyl)-2- methyl-1H-pyrazol-2-y-4-yl)benzylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate ¹ H NMR (D ₂ O) -1.06 (d, 3H), 1.20 (d, 3H), 1.70-1.71 (m, 2H), 1.78-1.79 (m, 2H), 1.86-1.87 (m, 1H), 2.06-2.07 (m, 2H), 2.22-2.23 (m, 1H), 2.59-2.60 ( m, 2H), 2.83-2.86 (m, 1H), 3.02 (s, 3H), 3.06 (s, 3H), 3.19 (m, 2H), 3.40-3 .43 (m, 2H), 3.53-3.54 (m, 2H), 3.63-3.64 (m, 1H), 3.85-3.86 (m, 2H), 4.27 -4.38 (m, 1H), 5.29-5.30 (d, 2H), 9.14 (s, 1H) C27H39N9O5S HPLC 94.7% (M+1) 602.1 599

(4R,5S,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(4-(1-(3-aminopropyl)-2- methyl-1H-pyrazol-2-y-4-yl)benzylthio)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate ¹ H NMR (D ₂ O) -1.08 (d, 3H), 1.22 (d, 3H), 1.72-1.73 (m, 2H), 1.80-1.81 (m, 2H), 1.88-1.89 (m, 1H), 2.08-2.09 (m, 2H), 2.24-2.25 (m, 1H), 2.61-2.62 ( m, 2H), 2.85-2.87 (m, 1H), 3.03 (s, 3H), 3.07 (s, 3H), 3.21 (m, 2H), 3.42-3 .45 (m, 2H), 3.55-3.56 (m, 2H), 3.64-3.65 (m, 1H), 3.87-3.88 (m, 2H), 4.29 -4.40 (m, 1H), 5.31-5.32 (d, 2H), 9.15 (s, 1H) C27H39N9O5S HPLC 90% (M+1) 602.1 600

(4S,5R,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(((3S,4S)-3-guanidino-4- hydroxypyrrolidin-1-yl)methyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.26 (d, 3H), 3.19-3.21 (m, 2H), 3.23 (m, 1H), 3 .47 (m, 1H), 3.51 (m, 1H), 3.84-3.86 (m, 1H), 3.98-4.05 (m, 1H), 4.12-4.16 (m, 2H), 4.22 (m, 2H), 4.49 (m, 1H), 5.30-5.46 (m, 2H), 9.25 (s, 1H) C19H28N10O5 HPLC 90% wt (M+1) 477.1

Example 600 Preparation of (4S,5R,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(((3S,4S)-3- guanidino-4-hydroxypyrrolidin-1-yl)methyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid

Preparation 28: (4S,5R,6R)-4-nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((isobutoxycarbonyloxy)methyl)-4 -methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

(R)-4-Nitrobenzyl 4-((2R,3R)-3-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-oxoazetidin-2-yl) -2-diazo-3-oxopentanoate (10 g, 20 mmol) was dissolved in 200 ml of acetone under N ₂ atmosphere. Rhodium octanoate (750 mg, 0.96 mmol) was added to this solution and heated at 60°C for 2.5 hours. Then, after completion of the reaction, the reaction mixture was cooled to -40°C and triflate anhydride (4.6 ml, 28 mmol), diisopropylethylamine (8.8 ml, 50.9 mmol) and a catalytic amount of dimethylaminopyridine (750 mg, 6 .14 mmol). Then, the reaction was stirred for 1 hour at -40°C. The reaction mixture was quenched by adding 0.1M phosphate buffer (pH=7). The aqueous layer was extracted with dichloromethane and the organic layer was evaporated in vacuo at room temperature to give a crude residue. Partial purification of the crude product was carried out by column chromatography, obtaining (4R,5R,6R)-4-nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl- 7-oxo-3-(trifluoromethylsulfonyloxy)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (2.7 g, 47%).

A mixture containing (4R,5R,6R)-4-nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-4-methyl-7-oxo-3- (trifluoromethylsulfonyloxy)-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate (2.6 g), tri-n-butylstannylmethanol (5.48 g, 17.1 mmol) and hexamethylphosphamide (degassed ), stirred for 30 minutes. To the mixture above was added a separately obtained solution containing tris(2-furyl)phosphine (0.32 g, 1.38 mmol), Pd(dba) ₃ (0.513 g, 0.56 mmol) and zinc chloride (0.513 g, 3. 77 mmol) in 10 ml hexamethylphosphamide (degassed) and heated at 70°C for 1 hour in a sealed tube. The reaction mixture was diluted with diethyl ether and water. The organic layer was separated and concentrated to give the crude product. The crude product was purified by column chromatography to give 1 g of (4S,5R,6R)-4-nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-( hydroxymethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate. ¹ H NMR CDCl ₃ 1.17 (d, 3H), 1.39 (d, 3H), 3.22-3.24 (m, 1H), 3.41-3.43 (m, 1H), 4 .09-4.12 (d, 1H), 4.34-4.37 (m, 1H), 4.38-4.39 (m, 1H), 4.58-4.62 (m, 1H) , 5.12-5.13 (d, 2H), 5.26-5.29 (dd, 1H), 5.49-5.52 (dd, 1H), 6.13 (br s, 1H), 7.64-7.66 (m, 2H), 8.22-8.24 (d, 2H), 8.93 (s, 1H).

A mixture of N,N-diisopropylethylamine (1.36 ml, 7.85 mmol) and dimethylaminopyridine (0.015 g, 0.13 mmol) in tetrahydrofuran (30 ml) was cooled to 0°C and isobutyl chloroformate (0.5 ml, 3.84 mmol) and stirred for 5 minutes. To the mixture above, was added a solution of (4S,5R,6R)-4-nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(hydroxymethyl)-4 -methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate (0.6 g, 1.24 mmol) dissolved in tetrahydrofuran (10 ml) at 0 °C , and continued stirring at room temperature for 24 hours. The reaction mixture was concentrated in vacuo, and the crude product was purified by column chromatography, obtaining the title compound, 0.4 g. ¹ H NMR CDCl ₃ -0.94-0.96 ( d, 6H), 1.18 (d, 3H), 1.38 (d, 3H), 1.94-2.01 (m, 1H), 3.10-3.11 (m, 1H), 3 .30-3.34 (m, 1H), 3.93-3.94 (d, 2H), 4.10-4.12 (d, 1H), 4.38-4.42 (m, 1H) , 4.78-4.82 (m, 1H), 5.17 (d, 2H), 5.25-5.29 (m, 1H), 5.47-5.51 (m, 2H), 6 .67-6.68 (br s, 1H), 7.63-7.65 (m, 2H), 8.23-8.25 (d, 2H), 8.87 (s, 1H).

Preparation 29: (4S,5R,6R)-4-nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-(((3S,4S)- 3-((E)-2,3-bis((4-nitrobenzyloxy)carbonyl)guanidino)-4-hydroxypyrrolidin-1-yl)methyl)-4-methyl-7-oxo-1-azabicyclo[3,2, 0]hept-2-ene-2-carboxylate

Pd(dba) ₃ CHCl ₃ (0.026 g, 0.025 mmol), triethyl phosphite (0.18 ml, 0.104 mmol) and 10 ml tetrahydrofuran-toluene (degassed, 1:9) were stirred for 30 minutes. To the mixture above was added a solution containing a mixture of 4-nitrobenzyl ((3S,4S)-4-hydroxypyrrolidin-3-ylamino)((4-nitrobenzyloxy)carbonylamino)methylenecarbamate trifluoroacetate salt (0.085 g, 0.102 mmol, neutralized with diisopropylethylamine) and (4S ,5R,6R)-4-nitrobenzyl 6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((isobutoxycarbonyloxy)methyl)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylate (0.1 g, 0.17 mmol) in 5 ml of tetrahydrofuran-toluene (degassed 1:9) and stirred at room temperature within 16 hours. The reaction mixture was diluted with ethyl acetate and 0.1M phosphate buffer 7.0. The organic layer was separated and washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated to give the crude product. The crude product was purified by column chromatography to give the title compound (0.06 g). ¹ H NMR CDCl ₃ 1.14 (d, 3H), 1.38 (d, 3H), 1.98-1.99 (m, 1H), 2.52-2.24 (m, 1H), 3 .08 (m, 1H), 3.34 (m, 1H), 3.41 (m, 1H), 4.06 (m, 1H), 4.11-4.13 (m, 1H), 4. 43 (m, 1H), 4.91-4.94 (m, 2H), 5.11-5.21 (m, 4H), 5.24-5.30 (m, 4H), 5.43- 5.49 (m, 2H), 6.65 (br s, 1H), 7.51-7.56 (m, 6H), 8.19-8.24 (m, 6H), 8.87 (s , 1H)

The compound above was hydrogenated analogously to step 4 of Example 298 to give the desired compound (4S,5R,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-( ((3S,4S)-3-guanidino-4-hydroxypyrrolidin-1-yl)methyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid . ¹ H NMR (D ₂ O) -1.16 (d, 3H), 1.26 (d, 3H), 3.19-3.21 (m, 2H), 3.23 (m, 1H), 3 .47 (m, 1H), 3.51 (m, 1H), 3.84-3.86 (m, 1H), 3.98-4.05 (m, 1H), 4.12-4.16 (m, 2H), 4.22 (m, 2H), 4.49 (m, 1H), 5.30-5.46 (m, 2H), 9.25 (s, 1H) C19H28N10O5 HPLC 90% wt (M+1) 477.1

601

(5R,6R)-6-((R)-1-(2-(1H-тетразол-1-ил)ацетамидо)этил)-3-((3S,5S)-5-(октагидро-1H-пирроло[3,2-c]пиридин-1-карбонил)пирролидин-3-илтио)-7-оксо-1-азабицикло[3,2,0]гепт-2-ен-2-карбоновая кислота

(5R,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(octahydro-1H-pyrrolo[ 3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid ¹ H NMR (D ₂ O) -1.32 (d, 3H), 1.68-1.69 (m, 1H), 1.83-1.87 (m, 2H), 1.97 (m, 1H), 2.12-2.17 (m, 3H), 2.48-2.52 (m, 1H), 2.64 (m, 3H), 3.00-3.07 (m, 3H) , 3.27-3.31 (m, 2H), 3.42-3.43 (d, 3H), 3.65-3.70 (m, 3H), 4.01 (m, 1H), 4 .11-4.13 (d, 1H), 4.28-4.30 (m, 1H), 4.37-4.40 (m, 1H), 4.53-4.57 (m, 1H) , 5.40 (d, 2H), 9.25 (s, 1H) C25H37N9O6S HPLC 90% wt 592.2 (M+1)

Example 601 Preparation of (5R,6R)-6-((R)-1-(2-(1H-tetrazol-1-yl)acetamido)ethyl)-3-((3S,5S)-5-(octahydro- 1H-pyrrolo[3,2-c]pyridine-1-carbonyl)pyrrolidin-3-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

Preparation 30 : 2-((2R)-3-((R)-1-(tert-butyldimethylsilyloxy)ethyl)-4-oxoazetidin-2-yl)acetic acid

To a solution of ( S )-4-phenyl-3-acetyl-2-oxazolidinone (42.8 g, 0.21 mol) in dichloromethane (250 ml) was added dropwise TiCl ₄ (50 g, 0.26 mol) over 30 minutes at -20--25°C. After the mixture was stirred for 30 minutes at -20--25°C, diisopropylethylamine (56 g, 0.24 mol) was added dropwise, and stirring was continued for 1 hour at the same temperature. To the mixture above was added ( 3R,4R)-4-acetoxy-3-[(R ) -1 -(( tert -butyldimethylsilyl)oxy)ethyl]-2-azetidinone (50 g, 0.17 mol) dissolved in dichloromethane (100 ml), at -15--10°C for 20 minutes. Then, the mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with dichloromethane (300 ml) and washed with water and brine. After drying over sodium sulfate, the organic layer was concentrated in vacuo to give a residue. The residue was purified by column chromatography (eluent 15% acetone in hexane) to give (4S)-3-(2-((2R)-3-((R)-1-(tert-butyldimethylsilyloxy)ethyl)-4-oxoazetidine- 2-yl)acetyl)-4-phenyloxazolidin-2-one (28.5 g). This compound (28.5 g) was dissolved in 300 ml of a mixture of acetone and water (2:1) and cooled to 0°C. Chilled hydrogen peroxide (30%, 22 ml) was added, followed by dropwise addition of 1N sodium hydroxide solution (200 ml) at 0°C over 30 minutes. After stirring for 15 minutes at the same temperature, the reaction was diluted with water (1 L). The aqueous layer was washed with ethyl acetate (500 ml×2). The aqueous layer was cooled to 0° C. and the pH was adjusted to 8 with 6 N HCl. The aqueous layer was washed with ethyl acetate (500 mL×2). The aqueous layer was acidified to pH 3 with dilute HCl and extracted with ethyl acetate (400 ml x 2). After drying over sodium sulfate, the organic layer was evaporated to give 2-((2R)-3-((R)-1-(tert-butyldimethylsilyloxy)ethyl)-4-oxoazetidin-2-yl)acetic acid, 11.5 g

¹ H NMR-CDCl ₃ -0.05 (d, 6H), 0.8 (s, 9H), 1.21 (d, 3H), 2.53-2.62 (m, 1H), 2.76 -2.78 (m, 1H), 2.82-2.84 (d, 1H), 3.96-3.98 (d, 1H), 4.12-4.14 (m, 1H), 6 .68 (br s, NH)

Scheme 1 was followed to prepare the compound below using the starting compound prepared above, (2-((2R)-3-((R)-1-(tert-butyldimethylsilyloxy)ethyl)-4-oxoazetidin-2-yl)acetic acid )

¹ H NMR (D ₂ O) -1.32 (d, 3H), 1.68-1.69 (m, 1H), 1.83-1.87 (m, 2H), 1.97 (m, 1H), 2.12-2.17 (m, 3H), 2.48-2.52 (m, 1H), 2.64 (m, 3H), 3.00-3.07 (m, 3H) , 3.27-3.31 (m, 2H), 3.42-3.43 (d, 3H), 3.65-3.70 (m, 3H), 4.01 (m, 1H), 4 .11-4.13 (d, 1H), 4.28-4.30 (m, 1H), 4.37-4.40 (m, 1H), 4.53-4.57 (m, 1H) , 5.40 (d, 2H), 9.25 (s, 1H), C25H37N9O6S, HPLC 90% wt 592.2 (M+1)

Antibacterial activity:

Compounds were evaluated for antibacterial activity against strains of Gram-positive and Gram-negative bacteria. These strains include methicillin-sensitive Staphylococcus aureus , carbapenem-sensitive Escherichia coli , Klebsiella pneumoniae , extended-spectrum ß-lactamase synthase (ESBL) SHV18 , K. pneumoniae, carbapenemase-synthesizing , genus Enterobacter; genus Morganello; genus Citrobacter; genus serratia; akinetobacter and carbapenem-sensitive Pseudomonas aeruginosa .

Experiments:

Antibacterial activity was assessed by determining the minimum inhibitory concentration (MIC) of these compounds by the broth microdilution method (CLSI manual, M7-A7/Jan 2006 , M100-S18/Jan 2008 ). Two-fold serial dilutions of test compounds in Mueller-Hinton medium were prepared in 96 well microtiter plates. An equal amount of Mueller-Hinton medium containing bacterial suspensions was added to these diluted solutions to give 5×10 ⁵ cfu per ml. The MICs of the test compounds were determined after keeping the microtiter plates at 35°C for 22 hours. The minimum concentration of a compound that inhibited visible bacterial growth was defined as the MIC.

Results:

The MICs of the test compounds are shown in Table 1.

Table 1: MICs of test compounds

Example Phenotype-organism MSSA ESBL+ve (SHV-18) KPC-2 ESBL-ve meropenem sensitive S. aureus ATCC29213 K. pneumoniae ATCC700603 K. pneumoniae ATCC BAA-1705 E. coli ATCC25922 P. aeruginosa ATCC27853 Data for MIC (µg/mL) one 8-16 -0.5-1 -2-4 0.25-1 32-64 5 eight >128 >128 eight >128 7 2-8 2-4 2-4 0.5 32-64 9 eight >128 >128 128 >128 ten 16 2 four one >128 eleven eight 64 32 four >128 12 eight 128 32 four >128 13 four eight four one 64 fourteen four four four 0.5 128 fifteen 2 16 16 one 128 16 four 64 16 four >128 17 four >128 32 16 128 eighteen eight 64 eight four 32 19 one eight >128 one 128 twenty 2 eight 16 one 128 21 2 four 4-16 2 >128 22 2 64-128 32 eight >128 23 16 one eight 0.5 32-128 24 16 one four 0.5 32-64 25 four eight eight one 128 26 four 4-8 eight one 128 27 16 one four 0.5 64-128 28 eight 2 4-8 2 4-8 29 four eight >128 one 128 thirty 2 eight eight one 128 31 16 16 four four >128 32 one one one 0.5 32 33 four 32 16 four >128 34 four eight eight one 128 35 one four 2-4 one >128 36 one 16 16 2 128 37 16 one 16 one >128 38 0.25 one 2-4 one 32-64 39 16 16 16 four 16 40 four eight 4-8 one >128 41 2 16 16 one >128 42 2 one eight one 128 43 2 four eight one 64 44 32 four eight four 16 45 one four 16 one four 46 one four eight one 16 47 2 128 64 2 >128 48 16 one 64 0.5 eight 49 2 2 >128 one >128 fifty one 8-16 2-4 1-2 16-32 51 eight 32 32 four >128 52 one 128 >128 eight >128 54 one >128 >128 eight >128 56 64 16 16 eight 64 57 32 16 128 four >128 58 32 >128 >128 16 >128 59 32 16 >128 2 32 60 32 32 64 16 >128 61 one 16 16 one >128 63 8-16 16-32 8-16 1-2 >128 64 2 eight eight 1-2 64 66 eight eight 4-8 2 >128 67 four >128 >128 eight >128 68 32 eight >128 four 32-64 70 16 eight 16 four >128 71 eight 128 64 16 >128 72 32 >128 >128 32 >128 73 four four eight 1-2 4-16 74 8-16 1-2 four 1-2 eight 75 four eight 16 one >128 76 2 eight eight one >128 77 4-8 one four 0.5-1 32-64 78 eight 2 >128 one 128 79 four >128 >128 32 >128 80 four 32 64 four >128 81 one eight eight one 64 82 eight 2 eight one 128 83 2 >128 >128 64 >128 84 four four 16 one 128 85 one 2 2 0.5 64 86 2 eight eight one 128 87 2 eight eight one 64 88 0.25 >128 >128 128 >128 89 0.5 eight four 0.5 128 90 one 32 four one 128 91 16 32 32 four >128 92 one four four 0.5 32 93 16 >128 >128 128 >128 94 0.25 >128 >128 64 >128 95 32 2 2 one 2 96 one 64 32 four >128 97 one 128 64 eight >128 98 32 32 32 eight >128 99 128 16 64 64 16 100 16 eight four one 32 101 2 one four 0.5 64 102 2 eight eight 2 64 103 0.5 four eight 0.5 eight 104 four one four 0.5 128 105 eight eight eight one 128 106 four four four one four 107 four four four one 16 108 2 four 16 one 128 109 eight four 16 four four 110 four 2 four 0.5 32 111 four 16 16 one >128 112 64 four four 2 eight 113 16 32 16 four >128 114 eight 2 four 0.5 >128 115 eight 2 eight 0.5 >128 116 eight 2 four 0.5 >128 117 2 2 four 0.5 >128 118 four 2 eight 0.5 64 119 2 one eight 0.5 16 120 2 four four 0.5 four 121 one four four 0.5 eight 122 one four four one 16 123 2 2 four 0.5 64 124 2 four four one four 125 2 32 16 2 128 126 2 eight eight 2 16 127 2 eight 16 2 32 128 16 eight eight four 64 129 32 32 eight four eight 130 2 eight four one 32 131 four 2 eight 0.5 16 132 2 four four one four 133 four four eight one eight 134 2 four four one 16 135 2 four four one eight 136 >128 16 16 four 32 137 four eight eight one >128 138 32 32 64 four >128 139 32 four four one 32 140 2 one 2 0.5 32 141 4-8 4-8 4-8 one 64 142 4-8 eight eight one 16-32 143 2 eight eight one 32-64 145 0.5 8-16 eight 2 32 146 1-4 1-2 2 one 64 147 2 2 4-8 one 64-128 148 1-2 one 2-4 0.5 32-64 149 2 eight eight one four 150 four 64 16 four 64 151 four 16 eight 2 32 153 eight 2 eight one 64 154 four 2 eight one 64 155 2 eight eight one 32 156 32 16 32 eight >128 157 2 eight four one four 158 2 four four one eight 159 2 four four one eight 160 four eight eight one 16 161 0.5 eight four 0.5 eight 162 one four four 0.5 16 163 one four four one eight 164 one one four 0.25 32 165 64 four 2 2 32 166 64 eight eight four 32 167 2 four four four 32 168 16 2 2 one 2 169 eight 16 2 one four 170 2 four eight one 32 171 2 128 128 four >128 172 four eight eight one 64 173 four 16 eight 2 16 174 four 16 eight 2 32 175 2 2 four one 16 176 2 four eight one eight 177 eight 2 2 2 32 178 32 four four 2 four 179 128 16 eight 2 16 180 128 32 32 four 16 181 >128 >128 64 eight 128 182 128 16 16 eight eight 183 eight 32 16 2 64 184 2 four eight 0.5 four 185 2 64 16 2 64 186 four four four 0.5 eight 187 four eight 64 2 128 188 128 16 eight eight 16 189 >128 32 eight four 16 190 64 16 four 2 four 191 64 32 eight eight 32 192 64 2 2 one four 193 64 eight four four eight 194 eight eight 16 2 16 195 2 one four 0.5 eight 196 2 four eight one 32 197 16 16 16 four 32 198 2 one four 0.25 32 199 32 four 2 one four 200 128 eight four 2 four 201 16 16 64 2 16 202 64 64 16 four eight 203 16 one four 0.5 128 204 32 >128 >128 eight >128 205 32 2 four one eight 206 64 four four four four 207 2 eight eight 2 >128 208 64 eight eight four >128 209 2 2 2 0.5 64 210 2 four four one 64 211 2 four four one 16 212 one 2 four 0.5 eight 213 one 2 four 0.5 eight 214 32 32 16 four >128 215 eight 32 eight 2 >128 216 32 16 four one four 217 16 one one 0.5 2 218 16 2 2 one 2 219 2 four four one four 220 32 2 2 one 2 221 32 2 2 2 four 222 64 eight four 2 eight 225 16 32 2 one 64 226 32 32 eight one 64 227 64 eight four 2 32 228 64 four eight one 64 229 128 64 64 16 32 230 32 eight four one eight 231 32 four 2 one 16 232 2 eight eight 2 >128 233 four four four one >128 234 0.5 four four 0.5 >128 235 2 - 16 2 >128 236 2 - four 2 128 237 one - four 2 128 238 16 - NT 16 >128 241 16 - 2 2 32 242 16 - 2 2 eight 243 32 - 32 16 >128 244 one - four one 64 245 eight - four 2 four 246 32 - 128 eight >128 247 32 - 32 four >128 248 one - four one >128 251 0.5 - 0.5 0.25 32 252 16 - four 2 16 253 32 - 16 16 16 254 64 - 16 eight 128 255 eight - eight four 32 256 four - 2 one 32 257 >128 - 16 four 128 258 one - 16 four 128 259 2 - 16 four >128 260 one - eight four 32 261 2 - 16 2 64 262 32 - 16 four 64 263 0.25 - 2 0.25 128 264 16 - four 2 eight 265 2 - eight 2 >128 266 64 - eight 2 128 267 0.5 - 2 one >128 268 eight - four 2 32 269 16 - four four 128 270 four - four one 64 271 2 - four one eight 272 128 - 64 64 >128 273 128 - 32 16 128 274 32 - 16 16 >128 275 64 - 64 16 >128 276 32 - four 2 eight 277 64 - four 2 16 278 16 - 2 2 four 279 >128 - 16 four >128 280 64 - eight eight 16 281 32 - 16 eight 64 282 32 - 2 one 32 283 16 - 0.5 0.25 eight 284 one - four one 64 285 64 - eight four 128 287 128 - eight four 16 288 128 - 16 four >128 289 eight - 16 eight >128 290 32 - four 2 eight 291 32 - 2 2 eight 292 128 - eight four 16 293 128 - 128 32 >128 294 one - one 0.06 16 295 16 - 16 2 64 296 four - 2 0.5 64 297 16 - 2 one four 298 one - one 0.125 one 299 16 - eight four 16 300 16 - four one 128 301 16 - 64 four >128 302 2 - 16 one 128 303 2 - 64 four >128 304 eight - four one >128 305 2 - one 0.25 eight 306 2 - one 0.25 four 307 one - four 0.25 128 309 16 - four one 32 310 32 - four one 64 311 32 - 32 eight >128 312 16 - four one 64 313 four - 16 one >128 314 four - 2 0.25 four 315 four - 2 0.125 64 316 four - 16 0.25 16 317 2 - eight 0.5 128 318 16 - 128 2 >128 319 2 - one 0.25 32 320 2 - four one 128 321 2 - eight one >128 322 16 - 16 2 >128 323 16 - eight 2 >128 324 four - four 0.5 four 325 eight - 64 four >128 326 2 - 16 one 64 327 one - 32 2 64 328 four - four 2 32 329 eight - 2 0.25 eight 330 eight - 2 0.25 64 331 four - four 0.25 eight 332 eight - four one eight 333 eight - four 0.5 four 334 four - 32 0.5 128 335 four - 64 one >128 336 four - four one eight 337 2 - one 0.5 32 338 eight - 32 2 128 339 eight - 32 one 32 340 eight - four one four 341 four - four one eight 342 16 - eight 2 eight 343 16 - eight 2 eight 344 16 - 16 one 16 345 64 - 32 eight 128 346 16 - eight one 16 347 four - 16 0.5 >128 348 eight - 16 one >128 349 four - four 0.25 32 350 2 - one 0.25 128 351 16 - four one >128 352 four - 2 0.25 2 353 16 - 2 0.25 16 354 2 - one 0.125 32 355 four - 16 one 128 356 four - 16 one >128 357 2 - 32 one >128 358 one - 32 one >128 359 eight - 2 0.5 16 360 eight - 2 0.5 one 361 eight four 2 one 2 362 eight four four 0.25 four 363 four 2 0.25 one 364 four 2 0.25 one 365 four 2 0.25 2 366 four 2 0.25 2 367 2 2 0.25 one 368 2 2 0.25 one 369 2 - eight 0.25 16 370 eight - 64 four >128 371 16 - four one 64 372 four - eight 0.5 64 373 four - >128 32 >128 374 eight - >128 32 >128 375 16 - eight 2 four 376 eight - 16 0.25 >128 377 four - 2 0.25 eight 378 four - 2 0.25 128 379 16 - 16 0.5 >128 380 32 - eight one 32 381 16 - four one >128 382 16 - four one 128 383 four - four 0.25 >128 384 four - four 0.5 64 385 four - 2 0.25 64 386 2 - eight 0.125 eight 387 eight - eight 0.25 32 388 eight - eight 2 >128 389 eight - four one >128 390 four - 16 one 128 391 one - 0.5 0.5 four 392 four - four one 64 393 four - one 0.125 eight 394 eight - 32 2 128 395 2 - one 0.125 one 396 four - one 0.125 four 397 2 - one 0.25 2 398 four - one 0.25 2 399 2 - 2 0.125 eight 400 four - one 0.125 one 401 eight - 2 0.5 2 402 one - one 0.06 32 403 four - eight 0.5 16 404 one - 0.5 0.25 one 405 four - 2 0.125 four 406 four - 2 0.25 16 407 2 - one 0.5 eight 408 four - 2 one 2 409 four - 2 one four 410 2 - four 0.5 four 411 2 - one 0.25 one 412 2 - 2 0.25 one 413 2 - 2 0.25 2 414 four - 2 0.5 four 415 four - one 2 16 416 four - 2 0.5 eight 417 eight - 2 0.5 16 418 eight - four one eight 419 four - one 0.25 one 420 four - one 0.25 2 421 four - 2 0.125 32 422 four - 2 0.25 four 423 eight - 2 0.5 32 424 16 - 2 0.25 16 425 four - 2 0.25 2 426 four - one 0.25 2 427 2 - one 0.25 2 428 four - four 0.5 2 429 four - 2 0.25 2 430 four - 2 0.5 four 431 2 - 0.5 0.25 one 432 2 - one 0.25 one 433 2 - one 0.25 one 434 2 - 2 0.5 2 435 2 - one 0.25 one 436 eight - one 0.25 eight 437 2 - one 0.25 2 438 2 - one 0.25 2 439 2 - one 0.25 one 440 2 - one 0.25 one 441 four - 2 0.25 eight 442 2 - one 0.125 0.5 443 four - 2 0.5 one 444 2 - 2 0.5 2 445 2 - one 0.25 one 446 2 - one 0.25 four 447 16 - four 0.5 16 448 four - eight 0.5 >128 449 four - four 0.5 64 450 eight - one 0.25 one 451 eight - one 0.25 2 452 2 - one 0.25 2 453 16 - 2 0.125 eight 454 eight - four 0.5 four 455 four - 2 0.5 four 456 2 - 2 0.5 2 457 2 - one 0.25 one 458 16 - one 0.5 16 459 one - one 0.125 2 460 four - 2 0.5 four 461 four - 2 0.5 four 462 four - one 0.25 2 463 four - one 0.5 2 464 four - four one 16 465 four - 2 0.5 16 466 four - 2 0.5 four 467 eight - 2 one eight 468 four - 2 0.5 eight 469 four - 2 0.5 four 470 four - 2 0.5 four 471 2 - 2 0.5 four 472 four - 2 0.5 2 473 four - 2 0.5 four 474 four - 2 0.25 2 475 four - 2 0.5 2 476 2 - 2 one 32 477 2 - 2 0.5 64 478 eight - one 0.125 eight 479 eight - 2 0.25 16 480 2 - one 0.25 2 481 2 - 2 0.125 2 482 four - four 0.25 four 483 four - four 0.5 128 484 2 - four one 32 485 eight - four 0.5 four 486 2 - eight 0.5 64 487 2 - one 0.25 eight 488 four - one 0.25 2 489 four - one 0.5 16 490 32 - 2 2 32 491 four - 2 0.25 eight 492 four - 2 0.5 2 493 2 - one 0.125 0.5 494 eight - four 0.25 16 495 2 - one 0.25 one 496 2 - 2 0.25 2 497 four - 2 0.25 four 498 2 - 2 0.125 eight 499 2 - one 0.25 one 500 2 - 2 0.25 2 501 four - one 0.25 one 502 four - one 0.25 2 503 2 - one 0.5 16 504 2 - four 0.5 32 505 2 - one 0.25 one 506 four - one 0.25 one 507 2 - eight one 64 508 16 - eight 2 128 509 32 - four four 32 510 four - four 0.25 one 511 four - 2 0.25 one 512 eight - 64 2 >128 513 four - one 0.25 16 514 16 - 16 0.5 32 515 2 - one 0.25 16 516 2 - 2 0.25 2 517 four - 2 0.5 four 518 eight - four one 128 519 16 - 16 2 >128 520 16 - 16 2 >128 521 2 - 0.5 0.5 2 522 four - 2 0.25 one 523 2 - one 0.125 one 524 four - 2 0.25 one 525 four - 2 0.25 0.5 526 four - 2 0.25 one 527 four - one 0.125 one 528 four - one 0.25 one 529 four - 2 0.25 one 530 2 - one 0.25 0.5 531 four - 2 0.125 one 532 four - 2 0.25 2 533 four - 2 0.25 2 534 2 - one 0.125 one 535 2 - 2 0.25 one 536 2 - 2 0.25 four 537 four - 2 0.25 2 538 four - 2 0.25 one 539 four - one 0.25 2 540 four - 2 0.25 one 541 2 - one 0.25 one 542 four - 2 0.25 2 543 2 - one 0.5 2 544 one - 0.5 0.25 one 545 one - 0.5 0.125 one 546 one - one 0.25 2 547 four - 2 0.5 2 548 eight - one 0.25 four 549 four - one 0.125 one 550 one - 2 0.25 eight 551 four - 2 0.25 2 552 four - 2 0.25 2 553 2 - one 0.25 2 554 four - 2 0.5 2 555 four - one 0.25 2 556 2 - one 0.125 four 557 four - four 0.125 16 558 16 - 2 0.5 128 559 one - one 0.25 four 560 one - 0.5 0.125 one 561 four - 2 0.5 eight 562 16 - 2 0.5 2 563 16 - 2 0.25 2 564 2 - one 0.125 one 565 2 - 2 0.25 one 566 0.5 - 0.5 0.06 0.25 567 one - 0.5 0.125 one 568 16 - 2 one four 569 2 - one 0.25 2 570 one - one 0.125 2 571 one - 0.5 0.06 one 572 four - 2 0.25 four 573 four - 2 0.125 one 574 eight - four 0.5 2 575 16 - 0.5 0.125 >128 576 one - 0.5 0.125 0.25 577 four - 2 0.25 four 578 2 - one 0.25 four 579 four - one 0.25 16 580 2 - one 0.25 0.5 581 eight - eight 0.5 64 582 2 - 2 0.25 0.5 583 one - one 0.03 0.5 584 2 - one 0.25 one 585 2 - one 0.125 four 586 four - one 0.25 2 587 four - 2 0.25 2 588 32 - four four four 589 four - 2 0.5 16 590 four - one 0.25 one 591 2 - one 0.25 one 592 2 - 0.5 0.125 0.5 593 16 - 32 one 128 594 one - >128 32 >128 595 eight - >128 four >128 596 2 - 16 one 32 597 four - 32 four 32 598 eight - 2 one 16 599 four - 2 one four 600 0.5 - four 0.5 16 601 2 - 64 2 128

Claims (665)

1. Compound of formula (I)

or its stereoisomer, internal salt or pharmaceutically acceptable salt: where: A is -NR ⁰ R; Z is -CH ₃ ; X is -S-; R ⁰ is hydrogen or C _1-6 alkyl which is optionally substituted with one or two substituents selected from the group consisting of halo, hydroxyl, cyano, carbamoyl, —SO ₂ NH ₂ and C _1-6 alkoxy; R represents: 1) -(CH ₂ ) _n C(=O)R ² , 2) -(CH ₂ ) _n C(=S)R ² , or 3) -(CH ₂ ) _n SO ₂ R ² , or R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from the group consisting of N, O and S; n is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5 and 6; R ¹ is -(CH ₂ ) _0-6 -HetC; ^R2 is: 1) C _1-6 alkyl substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, -CN, C _3-8 cycloalkyl, -NR ^a R ^b , -OC(=O)C _1-6 alkyl, -P(=O)(C _1-6 alkoxy) ₂ , -COOH, -COOC _1-6 alkyl, -SO ₂ C _1-6 alkyl, -S(=O)C _1-6 haloalkyl , -SCHF ₂ , HetA, AryA, -S-AryA, azetidine optionally substituted with oxo, hydroxyethyl or both, and azetidinone optionally substituted with C _1-6 hydroxyalkyl, 2) C _3-8 cycloalkyl substituted with C _1-6 haloalkyl or -NR ^x R ^y , 3) -(CH ₂ ) _0-3 -CR ^k =NOC _1-6 alkyl, optionally substituted with -COOR ^x , 4) -COOH, 5) C _1-6 haloalkyl, 6) C _1-6 haloalkoxy, 7) AryA or 8) HetA; R ⁴ is -COO ^- or -COOR ⁵ ; R ⁵ is hydrogen; Arya is: 1) a substituted or unsubstituted 5- or 6-membered aromatic ring with 1, 2, 3 or 4 heteroaromatic ring atoms independently selected from the group consisting of N, O and S, or 2) a substituted or unsubstituted 9- or 10-membered bicyclic aromatic ring with 1, 2, 3, 4, 5 or 6 heteroaromatic ring atoms independently selected from the group consisting of N, O and S; HetA is a substituted or unsubstituted 5-10 membered saturated ring with 1, 2, 3 or 4 heteroaromatic ring atoms independently selected from the group consisting of N, O and S, where any S atom in the ring is optionally oxidized; HetC is a substituted 4-8 membered saturated ring with 1 or 2 N ring atoms; R ^a is C _3-8 cycloalkyl, -CR ^x (=NR ^x ), -C(=NR ^x )N(R ^x ) ₂ , -(CH ₂ ) _1-6 OR ^x or -SO ₂ C _{1- 6} alkyl; R ^b is hydrogen or C _1-3 alkyl; ^Rc is: 1) H 2) -C _1-6 alkyl, optionally substituted with -NR ^h R ^j , -CN or -OH, 3) -(CH ₂ ) _1-3 C(=O)NR ^x R ^y , 4) -(CH ₂ ) _1-3 C (= O) NHCH ₂ CH ₂ OH, 5) -(CH ₂ ) _1-3 C(=O)NHOCH ₃ , 6) -(CH ₂ ) _1-3 C(=O)NHOBn, 7) -C _1-6 alkoxy, 8) pyridinyl, 9) -(CH ₂ ) _1-3 -pyrrolidinyl, optionally substituted with -C(=O)NR ^x R ^y , 10) tetrahydro-2H-pyran-4-yl, 11) -(CH ₂ ) _1-3 C(=O)-diazepanil, 12) -(CH ₂ ) _1-3 C(=O)-pyrrolidin-1-yl substituted with NR ^x R ^y , 13) -C(=NH)-pyrrolidin-1-yl, optionally substituted with NR ^x R ^y , 14) -(CH ₂ ) _1-3 -pyranyl optionally substituted with 1 or 2 substituents representing oxo or methoxy, 15) -(CH ₂ ) _1-3 -pyridinyl, optionally substituted with one or more groups selected from the group consisting of -CH ₃ , -OH and oxo, 16) -phenyl-C(=O)-pyrrolidinyl-NR ^x R ^y _, 17) -phenyl-C(=O)-piperazinyl or 18) -phenyl-(CH ₂ ) _1-3 -NR ^x R ^y ; R ^d is hydrogen, C _1-3 alkyl, C _1-3 hydroxyalkyl, or C _1-3 cyanoalkyl, or R ^c and R ^d are taken together with the N to which they are attached to give a substituted or unsubstituted 4-12 membered heterocyclic ring or ring system with 0, 1 or 2 additional heteroaromatic ring atoms independently selected from the group consisting of N, O and S, where the rings in the heterocyclic ring system may be bridged, fused, spiro-fused, or any combination of the two; where any ring nitrogen atom of a heterocyclic ring or ring system is optionally quadric-covalent; and where the heterocyclic ring or ring system is optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of: 1) -(CH ₂ ) _0-3 halogen, 2) oxo, 3) =NH, 4) -(CH ₂ ) _0-3 OH, 5) -C _1-6 alkyl optionally substituted with halogen, -CN and -OH, 6) -OC _1-6 alkyl, 7) -CH ₂ CH (OH) CH ₂ NH ₂ , 8) -CH ₂ CH(F)CH ₂ NH ₂ , 9) -C(=O)OH, 10) -(CH ₂ ) _0-3 NR ^h R ^j , optionally substituted with 1 or 2 -CH _3, -NH ₂ or halogen, 11) -NHCH ₂ CN, 12) -NHCH=NH, 13) -NHC(=O)R ⁱ , 14) -NHC(=O)(CH ₂ ) _0-2 NHC(=NH)NH ₂ , 15) -C (= NH) NH ₂ , 16) -C(=O)C _1-6 aminoalkyl, optionally substituted with -OH, 17) -(CH ₂ ) _0-2 C(=O)(CH ₂ ) _0-2 NR ^h R ^j , optionally substituted with -NH ₂ or -OH, 18) -(CH ₂ ) _0-2 C(=O)CH(NH ₂ )(CH ₂ ) _0-2 OH, 19) -C(=O)NH(CH ₂ ) _1-3 NH ₂ , optionally substituted with -OH, 20) -C(=O)(CH₂)_1-3NH₂, optionally substituted -NH₂, 21) -C (= O) (CH ₂ ) _0-3 NHC (= NH) NH ₂ , 22) -(CH ₂ ) _0-1 NHCH ₂ CH ₂ NR ^h R ^j , 23) -(CH ₂ ) _0-3 NHC(=NH)NH ₂ , 24) -(CH ₂ ) _0-1 NH(CH ₂ ) _0-1 C(=O)(CH ₂ ) _0-1 NR ^h R ^j , 25) -(CH ₂ ) _0-1 NHSO ₂ (CH ₂ ) _0-2 NR ^h R ^j , 26) -(CH ₂ ) _0-2 NHSO ₂ CH ₃ , 27) -ONH ₂ , 28) -ONHC(=O)CH ₂ NHCH ₃ , 29) -C(=O)NH-pyridinyl, 30) -C(=O)-diazepinyl optionally substituted with -C(=NH)NH ₂ , 31) -C(=O)-piperazinyl, 32) -(CH ₂ ) _0-1 C(=O)-pyrrolidinyl optionally substituted with -NH ₂ , 33) -NHCH ₂ -pyridinyl optionally substituted with one or more groups selected from the group consisting of oxo, -CH ₃ and -OH, 34) -NH-pyrimidinyl, 35) -(CH ₂ ) _0-1 -phenyl, 36) -(CH ₂ ) _0-2 -piperazinyl, 37) -(CH ₂ ) _0-2 azetidinyl optionally substituted with -CH ₂ NH ₂ , -NH ₂ , piperazinyl or -OH, 38) -(CH ₂ ) _0-2 pyrrolidinyl, optionally substituted with -NH ₂ , 39) -(CH ₂ ) _0-2 triazolyl optionally substituted with -CH ₂ NH ₂ and 40) -(CH ₂ ) _0-2 tetrazolyl; R ^f is H, -C(=O)N(C _1-6 alkyl) ₂ , -SO ₂ C _1-6 alkyl, -SO ₂ N(R ^x ) ₂ , -C(=O)-cyclopentyl- N(R ^x ) ₂ , -C(=O)-pyridinyl optionally substituted with one or more groups selected from the group consisting of oxo, -C ₁ - ₃ alkyl and -OH, -C(=O)-pyrrolidinyl, substituted with -NR ^a R ^b or halogen, -C(=O)-thiazolidinyl, -SO ₂ -piperazine or -SO ₂ -pyrrolidinyl-N(R ^x ) ₂ ; R ^g is hydrogen or C _1-3 alkyl, or R ^f and R ^g are taken together with the N to which they are attached to give a group selected from the group consisting of morpholinyl, piperazinyl, pyrrolidinyl optionally substituted with -CH ₃ , piperidinyl or thiomorpholinyl optionally substituted with -C _1-6 alkyl or - N(R ^x ) ₂ , and triazolyl substituted with -CH ₂ NH ₂ ; R ^h and R ^j are independently H, C _1-6 alkyl or C _3-8 cycloalkyl; R ⁱ is C _1-5 aminoalkyl, -OC _1-6 alkyl, -C _1-3 cyanoalkyl or -C _1-6 haloalkyl optionally substituted with -NR ^x R ^y ; R ^k is C _1-6 alkyl or thiazole substituted with -NH ₂ ; each R ^x and R ^y is independently hydrogen or C _1-3 alkyl; and where, when HetA, AryA, HetC or the rings formed by the combination of R and R ⁰ are substituted, the substituents are 1-4 members selected from the group consisting of: 1) halogen, 2) -OH, 3) oxo, 4) -COOH, 5) -COOC _1-6 alkyl, 6) C _1-6 alkyl, optionally substituted with -NR ^f R ^g , 7) C _1-6 alkoxy, 8) -(CH ₂ ) _0-3 OC _1-3 alkyl, 9) C _1-6 haloalkyl, 10) C _1-6 hydroxyalkyl, 11) C ₃ -C ₈ cycloalkyl, 12) -C(=O)C _1-6 alkyl, 13) -C(=O)C _1-6 aminoalkyl, 14) -C(=O)NR ^c R ^d , 15) -(CH ₂ ) _0-1 NR ^x R ^y , 16) -(CH ₂ ) _0-3 NR ^f R ^g , 17) -(CH ₂ ) _1-3 -C(=O)NR ^x R ^y , 18) -NHCH ₂ CN, 19) -NHC(=O)R ⁱ , 20) -(CH ₂ ) _0-1 NHSO ₂ NR ^x R ^y , 21) -SO ₂ NR ^c R ^d , 22) -CH=NH, 23) -(CH ₂ ) _0-3 C(=NH)NH ₂ , 24) -(CH ₂ ) _0-3 NHC(=NH)NH ₂ , 25) -(CH ₂ ) _0-2 -thienyl, 26) -(CH ₂ ) _0-2 -tetrazolyl, 27) -(CH ₂ ) _0-2 -thiazolyl, 28) -(CH ₂ ) _0-2 -pyridinyl, optionally substituted with -CH ₃ or quaternized with -CH ₃ or CH ₂ CONH ₂ , 29) -(CH ₂ ) _0-2 -triazolyl, 30) -(CH ₂ ) _0-2 -piperidinyl optionally substituted with -CH ₃ or quaternized with -CH ₃ or -(CH ₂ ) _0-3 NH _2, 31) -(CH ₂ ) _0-2 -pyrazolyl optionally substituted with one or more - (CH ₂ ) _0-3 NH ₂ and further optionally quaternized with -CH _3, 32) -(CH ₂ ) _1-3 -C(=O)-pyrrolidinyl optionally substituted with -NR ^x R ^y , 33) -(CH ₂ ) _0-2 -pyrrolidinyl optionally substituted with -NR ^x R ^y , 34) -C(=NH)-pyrrolidinyl optionally substituted with -NR ^x R ^y , 35) 4,5-dihydrothiazol-2-yl, and 36) -CON(CH ₃ )CH ₂ CH ₂ C(=O)-pyrrolidin-1-yl substituted with NH ₂ or diazepanil. 2. Compound according to claim 1 of formula (Ib)

or its stereoisomer, internal salt or pharmaceutically acceptable salt, where: A is -NR ⁰ R; R ⁰ is hydrogen or C _1-6 alkyl which is optionally substituted with one or two substituents selected from the group consisting of halo, hydroxyl, cyano, carbamoyl, -SO ₂ NH ₂ and C _1-6 alkoxy; R represents: 1) -(CH ₂ ) _n C(=O)R ² , 2) -(CH ₂ ) _n C(=S)R ² , 3) -(CH ₂ ) _n SO ₂ R ² , R and R ⁰ , together with the N to which they are attached, form a substituted or unsubstituted 5-6 membered cyclic ring with 0, 1, 2, 3 or 4 additional heteroaromatic ring atoms independently selected from the group consisting of N, O and S; n is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5 and 6; R ¹ is -(CH ₂ ) _0-6 -HetC; R ² is C _1-6 alkyl substituted with AryA or -S-AryA; R^four represents -COO^- or -COOR⁵; R ⁵ is hydrogen; AryA is a substituted or unsubstituted 5-membered aromatic ring with 3 or 4 N ring atoms; HetC is a substituted 4-8 membered saturated ring with 1 N ring atom; R ^a is C _3-8 cycloalkyl, -CR ^x (=NR ^x ), -C(=NR ^x )N(R ^x ) ₂ or -SO ₂ C _1-6 alkyl; R ^b is hydrogen or C _1-3 alkyl; ^Rc represents 1) H 2) -C _1-6 alkyl, optionally substituted with -NR ^h R ^j , -CN or -OH, 3) -(CH ₂ ) _1-3 C(=O)NR ^x R ^y , 4) -(CH ₂ ) _1-3 C (= O) NHCH ₂ CH ₂ OH, 5) -(CH ₂ ) _1-3 C(=O)NHOCH ₃ , 6) -(CH ₂ ) _1-3 C(=O)NHOBn, 7) -C _1-6 alkoxy, 8) pyridinyl, 9) -(CH ₂ ) _1-3 -pyrrolidinyl, optionally substituted with -C(=O)NR ^x R ^y , 10) tetrahydro-2H-pyran-4-yl, 11) -(CH ₂ ) _1-3 C(=O)-diazepanil, 12) -(CH ₂ ) _1-3 C(=O)-pyrrolidin-1-yl, optionally substituted with NR ^x R ^y , 13) -C(=NH)-pyrrolidin-1-yl, optionally substituted with NR ^x R ^y , 14) -(CH ₂ ) _1-3 -pyranyl optionally substituted with 1 or 2 substituents which are oxo or methoxy, 15) -(CH ₂ ) _1-3 -pyridinyl, optionally substituted with one or more groups selected from the group consisting of -CH ₃ , -OH, and oxo, 16) -phenyl-C(=O)-pyrrolidinyl-NR ^x R ^y , 17) -phenyl-C(=O)-piperazinyl or 18) -phenyl-(CH ₂ ) _1-3 -NR ^x R ^y ; R ^d is hydrogen, C _1-3 alkyl, C _1-3 hydroxyalkyl, or C _1-3 cyanoalkyl, or R ^c and R ^d are taken together with the N to which they are attached to give a substituted or unsubstituted 4-12 membered heterocyclic ring or ring system with 0, 1 or 2 additional heteroaromatic ring atoms independently selected from the group consisting of N, O and S, where the rings in the heterocyclic ring system may be bridged, fused, spiro-fused, or any combination of the two; where any ring nitrogen atom of a heterocyclic ring or ring system is optionally quadric-covalent; and where the heterocyclic ring or ring system is optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of: 1) -(CH ₂ ) _0-3 -halogen, 2) oxo, 3)=NH, 4) -(CH ₂ ) _0-3 -OH, 5) -C _1-6 alkyl, optionally substituted with -OH, halogen or cyano, 6) -OC _1-6 alkyl, 7) -CH ₂ CH (OH) CH ₂ NH ₂ , 8) -CH ₂ CH(F)CH ₂ NH ₂ , 9) -C(=O)OH, 10)-(CH₂)_0-3NR^hR^j, optionally substituted with 1 or 2 -CH₃,-NH₂or halogen 11) -NHCH ₂ CN, 12) -NHCH=NH, 13) -NHC(=O)R ⁱ , 14) -NHC(=O)(CH ₂ ) _0-2 NHC(=NH)NH ₂ , 15) -C (= NH) NH ₂ , 16) -C(=O)C _1-6 aminoalkyl, optionally substituted with -OH, 17) -(CH ₂ ) _0-2 C(=O)(CH ₂ ) _0-2 NR ^h R ^j , optionally substituted with -NH ₂ or -OH, 18) -(CH ₂ ) _0-2 C(=O)CH(NH ₂ )(CH ₂ ) _0-2 OH, 19) -C(=O)NH(CH ₂ ) _1-3 NH ₂ , optionally substituted with -OH, 20) -C(=O)(CH ₂ ) _1-3 NH ₂ , optionally substituted with -NH ₂ , 21) -C (= O) (CH ₂ ) _0-3 NHC (= NH) NH ₂ , 22) -(CH ₂ ) _0-1 NHCH ₂ CH ₂ NR ^h R ^j , 23) -(CH ₂ ) _0-3 NHC(=NH)NH ₂ , 24) -(CH ₂ ) _0-1 NH(CH ₂ ) _0-1 C(=O)(CH ₂ ) _0-1 NR ^h R ^j , 25) -(CH ₂ ) _0-1 NHSO ₂ (CH ₂ ) _0-2 NR ^h R ^j , 26) -(CH ₂ ) _0-2 NHSO ₂ CH ₃ , 27) -ONH ₂ , 28) -ONHC(=O)CH ₂ NHCH ₃ , 29) -C(=O)NH-pyridinyl, 30) -C(=O)-diazepinyl optionally substituted with -C(=NH)NH ₂ , 31) -C(=O)-piperazinyl, 32) -(CH ₂ ) _0-1 -C(=O)-pyrrolidinyl optionally substituted with -NH ₂ , 33) -NHCH ₂ -pyridinyl optionally substituted with one or more groups selected from the group consisting of -CH ₃ , -OH and oxo, 34) -NH-pyrimidinyl, 35) -(CH ₂ ) _0-1 -phenyl, 36) -(CH ₂ ) _0-2 -piperazinyl, 37) -(CH ₂ ) _0-2 azetidinyl, optionally substituted with -NH ₂ , -CH ₂ NH ₂ , piperazinyl or -OH, 38) -(CH ₂ ) _0-2 pyrrolidinyl, optionally substituted with -NH ₂ , 39) -(CH ₂ ) ₀ -triazolyl optionally substituted with -CH ₂ NH ₂ , and 40) -(CH ₂ ) _0-2 tetrazolyl; ^Rf is: 1) H 2) -C (= O) N (C _1-6 alkyl) ₂ , 3) -SO ₂ C _1-6 alkyl, 4) -SO ₂ N(R ^x ) ₂ , 5) -C (= O) -cyclopentyl-N (R ^x ) ₂ , 6) -C(=O)-pyridinyl optionally substituted with one or more groups selected from the group consisting of oxo, -C _{1 -3} alkyl and -OH, 7) -C(=O)-pyrrolidinyl substituted with -NR ^a R ^b or halogen, 8) -C(=O)-thiazolidinyl; -SO ₂ -piperazine or 9) -SO ₂ -pyrrolidinyl-N(R ^x ) ₂ ; R ^g is hydrogen or C _1-3 alkyl; or R ^f and R ^g are taken together with the N to which they are connected to give a group selected from the group consisting of morpholinyl, piperazinyl, pyrrolidinyl, optionally substituted with -CH ₃ ; piperidinyl or thiomorpholinyl optionally substituted with -C _1-6 alkyl or -N(R ^x ) ₂ and triazolyl substituted with -CH ₂ NH ₂ ; R ^h and R ^j are independently H, C _1-6 alkyl or C _3-8 cycloalkyl; R ⁱ is -C _1-5 aminoalkyl, -OC _1-6 alkyl, -C _1-3 cyanoalkyl or -C _1-6 haloalkyl optionally substituted with -NR ^x R ^y ; each R ^x and R ^y is independently hydrogen or C _1-3 alkyl; where, when AryA, HetC or rings formed by combining R and R ⁰ are substituted, the substituents are 1-4 members selected from the group consisting of: 1) halogen, 2) -OH, 3) oxo, 4) -COOH, 5) -COOC _1-6 alkyl, 6) C _1-6 alkyl, optionally substituted with -NR ^f R ^g , 7) C _1-6 alkoxy, 8) -(CH ₂ ) _0-3 OC _1-3 alkyl, 9) C _1-6 haloalkyl, 10) C _1-6 hydroxyalkyl, 11) C ₃ -C ₈ cycloalkyl, 12) -C(=O)C _1-6 alkyl, 13) -C(=O)C _1-6 aminoalkyl, 14) -C(=O)NR ^c R ^d , 15) -(CH ₂ ) _0-1 NR ^x R ^y , 16) -(CH ₂ ) _0-3 NR ^f R ^g , 17) -(CH ₂ ) _1-3 -C(=O)NR ^x R ^y , 18) -NHCH ₂ CN, 19) -NHC(=O)R ⁱ , 20) -(CH ₂ ) _0-1 NHSO ₂ NR ^x R ^y , 21) -SO ₂ NR ^c R ^d , 22) -CH=NH, 23) -(CH ₂ ) _0-3 C(=NH)NH ₂ , 24) -(CH ₂ ) _0-3 NHC(=NH)NH ₂ , 25) -(CH ₂ ) _0-2 -thienyl, 26) -(CH ₂ ) _0-2 -tetrazolyl, 27) -(CH ₂ ) _0-2 -thiazolyl; 28) -(CH ₂ ) _0-2 -pyridinyl, optionally substituted with -CH ₃ or quaternized with -CH ₃ or CH ₂ CONH ₂ , 29) -(CH ₂ ) _0-2 -triazolyl, and 30) -(CH ₂ ) _0-2 -piperidinyl, optionally substituted with -CH ₃ or quaternized with -CH ₃ or -(CH ₂ ) _0-3 NH ₂ , 31) -(CH ₂ ) _0-2 -pyrazolyl optionally substituted with one or more -(CH ₂ ) _0-3 NH ₂ and further optionally quaternized with -CH ₃ , 32) -(CH ₂ ) _1-3 -C(=O)-pyrrolidinyl optionally substituted with -NR ^x R ^y , 33) -(CH ₂ ) _0-2 -pyrrolidinyl optionally substituted with -NR ^x R ^y , 34) -C(=NH)-pyrrolidinyl optionally substituted with -NR ^x R ^y , and 35) 4,5-dihydrothiazol-2-yl. 3. The compound according to claim 1 or 2 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where A represents -NR ⁰ R, and HetC is a substituted pyrrolidine and the substituents are 1 to 4 members selected from the group consisting of: 1) halogen, 2) -OH, 3) oxo, 4) -COOH, 5) -COOC _1-6 alkyl, 6) C _1-6 alkyl, optionally substituted with -NR ^f R ^g , 7) C _1-6 alkoxy, 8) -(CH ₂ ) _0-3 OC _1-3 alkyl, 9) C _1-6 haloalkyl, 10) C _1-6 hydroxyalkyl, 11) C ₃ -C ₈ cycloalkyl, 12) -C(=O)C _1-6 alkyl, 13) -C(=O)C _1-6 aminoalkyl, 14) -C(=O)NR ^c R ^d , 15) -(CH ₂ ) _0-3 NR ^f R ^g , 16) -NHCH ₂ CN, 17) -NHC(=O)R ⁱ , 18) -(CH ₂ ) _0-1 NHSO ₂ NR ^x R ^y , 19) -SO ₂ NR ^c R ^d , 20) -CH=NH, 21) -(CH ₂ ) _0-2 -thienyl, 22) -(CH ₂ ) _0-2 -tetrazolyl, 23) -(CH ₂ ) _0-2 -thiazolyl; 24) -(CH ₂ ) _0-2 -pyridinyl, optionally substituted with -CH ₃ or quaternized with -CH ₃ or CH ₂ CONH ₂ , 25) -(CH ₂ ) _0-2 -triazolyl, and 26) 4,5-dihydrothiazol-2-yl. 4. Connection according to paragraphs. 1, 2 or 3 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where: R ⁰ is hydrogen or methyl; R represents 1) -(CH ₂ ) _n C(=O)R ² or 2) -(CH ₂ ) _n SO ₂ R ² , or R and R ⁰ , together with the N to which they are connected, form 1) [1,2,3]triazolyl substituted with C _1-6 alkyl, where C _1-6 alkyl is substituted with halogen, -NR ^x R ^y , -OH or C _1-3 alkoxy, or 2) tetrazolyl, optionally substituted with -NR ^x R ^y . 5. Connection according to any one of paragraphs. 1-4 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where n is 0 or 1. 6. The compound according to claim 5 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where n is 0. 7. The connection according to any one of paragraphs. 1-6 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where R ¹ represents -(CH ₂ ) _0-1 -HetC. 8. Connection according to any one of paragraphs. 1-7 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where HetC is a pyrrolidine with 1 substituent independently selected from the group consisting of -(CH ₂ ) _0-3 NR ^f R ^g , -(CH ₂ ) _1-3 -(C=O)-pyrrolidinyl optionally substituted with -NR ^x R ^y , -C(=NH)-pyrrolidinyl optionally substituted with -NR ^x R ^y , -(CH ₂ ) _0-3 C(=NH)NH ₂ , -(CH ₂ ) _0-3 NHC(=NH)NH ₂ , -C(=O)NR ^c R ^d and -SO ₂ NR ^c R ^d , where: R ^f is -C(=O)-pyrrolidinyl substituted with -NR ^a R ^b or halogen, or -SO ₂ -pyrrolidinyl-N(R ^x ) ₂ ; R ^a is -CR ^x (=NR ^x ), -C(=NR ^x )N(R ^x ) ₂ , -(CH ₂ ) _1-6 OR ^x or -SO ₂ C _1-6 alkyl; R ^b is hydrogen or C _1-3 alkyl; R ^x is hydrogen or C _1-3 alkyl; R ^g is hydrogen or C _1-3 alkyl, or R ^f and R ^g are taken together with the N to which they are connected to give a group selected from the group consisting of pyrrolidinyl optionally substituted with -CH ₃ . 9. Connection according to any one of paragraphs. 1-8 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where: ^Rc is: 1) -C _1-6 alkyl, optionally substituted with -NR ^h R ^j , pyrrolidinyl or -OH, 2) pyridinyl, 3) pyrrolidinyl, optionally substituted with -C(=O)NR ^x R ^y , 4) -C(=NH)-pyrrolidin-1-yl, optionally substituted with NR ^x R ^y , 5) -CH ₂ CH ₂ C(=O)-pyrrolidin-1-yl, optionally substituted with NR ^x R ^y , 6) -phenyl-C(=O)-piperazinyl, 7) -phenyl-CH ₂ -NR ^x R ^y or 8) -phenyl-C(=O)-pyrrolidinyl-NR ^x R ^y _; R ^d is hydrogen or C _1-3 alkyl; or R ^c and R ^d are taken together with the N they are connected to, getting: a) a 4-8 membered heterocyclic ring with 0, 1 or 2 additional heteroaromatic ring atoms independently selected from the group consisting of N, O and S, or b) a 6-12 membered heterocyclic bi- or tricyclic ring with 0, 1 or 2 additional heteroaromatic ring atoms independently selected from the group consisting of N, O and S, wherein the bicyclic ring is optionally bridged, fused or spirocyclic, or is any combination of the two, and where any ring nitrogen atom of the heterocyclic ring or heterocyclic bicyclic ring is optionally quadric-covalent; and where the heterocyclic ring or heterocyclic bicyclic ring is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of: 1) halogen, 2) -C _1-6 alkyl optionally substituted with 1 or 2 substituents selected from the group consisting of halogen, -CN and -OH, 3) -C (= NH) NH ₂ , 4) -(CH ₂ ) _0-2 C(=O)(CH ₂ ) _0-2 NR ^h R ^j , optionally substituted with -NH ₂ or -OH, 5) -(CH ₂ ) _0-3 NR ^h R ^j , optionally substituted with -NH ₂ or halogens, 6) -C(=O)C _1-6 aminoalkyl, optionally substituted with -OH, 7) -C(=O)OH, 8) -C (= O) (CH ₂ ) _0-3 NHC (= NH) NH ₂ , 9) -(CH ₂ ) _0-1 NHCH ₂ CH ₂ NR ^h R ^j , 10) -(CH ₂ ) _0-3 NHC(=NH)NH ₂ , 11) -(CH ₂ ) _0-1 NH(CH ₂ ) _0-1 C(=O)(CH ₂ ) _0-1 NR ^h R ^j , 12) -(CH ₂ ) _0-1 NHSO ₂ (CH ₂ ) _0-2 NH ₂ , 13) -(CH ₂ ) _0-2 NHSO ₂ CH ₃ , 14) -NR ^h R ^j , 15) -NHCH ₂ CN, 16) -NHCH=NH, 17) -NHC(=O)R ⁱ , 18) -NHSO ₂ N (CH ₃ ) ₂ , 19) -NHC(=O)CH ₂ NHC(=NH)NH ₂ , 20) -OH, 21) -OC _1-6 alkyl, 22) -ONH ₂ , 23) -ONHC(=O)CH ₂ NHCH ₃ , 24) oxo, 25) =NH, 26) -(CH ₂ ) _0-1 -phenyl, 27) -(CH ₂ ) _0-2 -piperazinyl, 28) -C(=O)NH-pyridinyl, 29) -C(=O)-piperazinyl, 30) -C(=O)-pyrrolidinyl, optionally substituted with -NH ₂ , 31) azetidinyl optionally substituted with -CH ₂ NH ₂ , -NH ₂ , piperazinyl or -OH, 32) pyrrolidinyl, optionally substituted with -NH ₂ , 33) -NHCH ₂ -pyridinyl substituted with oxo, -CH ₃ , and -OH, 34) -NH-pyrimidinyl, 35) triazolyl optionally substituted with -CH ₂ NH ₂ , and 36) tetrazolyl. 10. The compound according to claim 1 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where R ⁰ is hydrogen and R is: 1) -C(=O)CHF ₂ , 2) -C (= O) CF ₃ , 3) -C(=O)CH ₂ CF ₃ , 4) -C (= O) CF ₂ CF ₃ , 5) -C(=O)CF ₂ C _1-5 alkyl, 6) -C(=O)CHFCH ₃ , 7) -C (= O) CF ₂ CH ₂ OH, 8) -C (= O) CH ₂ OH, 9) -C(=O)CH ₂ OCOCH ₃ , 10) -C (= O) CH ₂ CN, 11) -C (= O) CH ₂ SO ₂ C _1-6 alkyl _, 12) -C(=O)CH ₂ SCHF ₂ , 13) -C(=O)CH ₂ S(=O)CHF ₂ , 14) -C(=O)CH ₂ P(=O)(OCH ₃ ) ₂ , 15) -C(=O)CH ₂ S-tetrazole, optionally substituted with -CH ₃ , 16) -C (= O)CH ₂ -thienyl, 17) -C (= O) CH (NH ₂ ) CH ₂ -tetrazole, 18) -C (= O) CH (NH ₂ ) CH ₂ -pyrazole, 19) -C(=O)CH ₂ -tetrazole optionally substituted with -C(CH ₃ ) ₃ , -CF ₃ , -CHF ₂ , -CH ₃ , NH ₂ -COOC _1-6 alkyl, thienyl, -CH ₂ NHCH ₃ , -NH ₂ or -COOEt, 20) -C(=O)CH ₂ -triazole, optionally substituted with -CH ₃ and -CF ₃ , or -CF ₃ and -NH ₂ , 21) -C (= O) C (CH ₃ ) ₂ -tetrazole, 22) -C (= O) CH ₂ -azetidine, 23) -C(=O)CH(CH ₃ )-azetidine optionally substituted with oxo, hydroxyethyl or both, 24) -C(=O)CH ₂ -pyrrolidinyl optionally substituted with one or more of -F or -CH ₂ NHCH ₃ , 25) -C (= O) CF ₂ -thienyl, 26) -C(=O)-C _1-6 alkyl-NR ^a R ^b , 27) -C(=O)-pyrrolidinyl optionally substituted with F or NH ₂ , 28) -C (= O) -tetrahydrofuran, 29) -C(=O)-(CH ₂ ) _0-1 piperazine, 30) -C(=O)-pyrazine, 31) -C(=O)-thiazolidine optionally substituted with one or more oxo, 32) -C(=O)-pyrazole, optionally substituted with CH ₃ and CF ₃ , 33) -C(=O)CHFC _1-5 alkyl, 34) -C(=O)CH(OH)C _1-5 alkyl, 35) -C (= O) CR ^k \u003d NOC (CH ₃ ) ₂ COOH, 36) -C(=O)CR ^k = NOCH ₃ , 37) -C(=O)C(=O)OH, 38) -(CH ₂ ) _0-6 C(=O)OH, 39) -(CH ₂ ) _0-6 C(=O)(CH ₂ ) _1-6 OH, 40) -C(=O)OCH ₂ CHF ₂ , 41) -C(=O)OCH ₂ CF ₃ , 42) -C(=O)-C_3-6cycloalkyl substituted with CF₃or NH₂, or R and R ⁰ , together with the N to which they are attached, form a [1,2,3-]triazole, optionally substituted with -CH ₂ OH, -CH ₂ OCH ₃ , -CH ₂ F, -CH ₂ NH ₂ , - CH ₂ NHCH ₃ , -C(=O)OCH ₃ , or tetrazole optionally substituted with -NH ₂ . 11. The compound according to claim 1 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where NR ⁰ R is:

,

,

,

,

,

,

,

,

,

,

,

,

,

or

. 12. The compound according to claim 1 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where R ⁰ is hydrogen and R is: 1) -C(=O)CH ₂ S-tetrazole, optionally substituted with -CH ₃ , 2) -C(=O)CH ₂ -tetrazole optionally substituted with -C(CH ₃ ) ₃ , -CF ₃ , -CHF ₂ , -CH ₃ , NH ₂ -COOC _1-6 alkyl, thienyl, -CH ₂ NHCH ₃ , -NH ₂ or -COOEt, or 3) -C(=O)CH ₂ -triazole, optionally substituted with -CH ₂ NR ^a R ^b or -CH ₃ and -CF ₃ , or -CF ₃ and -NH ₂ , R and R ⁰ are taken together with the N to which they are connected to give a [1,2,3-]triazole optionally substituted with -CH ₂ OH, -CH ₂ OCH ₃ , -CH ₂ F, -CH ₂ NH ₂ , - CH ₂ NHCH ₃ , -C(=O)OCH ₃ , or tetrazole optionally substituted with -NH ₂ . 13. The compound according to claim 1 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where R ⁰ is hydrogen and R is -C(=O)CH ₂ -tetrazolyl, R and R ⁰ are combined together to give triazolyl optionally substituted with -CH ₂ -OH. 14. The compound according to p. 1 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where R ¹ represents: 1) pyrrolidinyl substituted with 1 or 2 of a) -CONR ^c R ^d , b) -CON(CH ₃ )CH ₂ CH ₂ C(=O)-pyrrolidin-1-yl substituted with NH ₂ or diazepanil, c) -CH ₂ NR ^f R ^g , d) -CH=NH, e) F f) -(CH ₂ ) _0-1 NHC(=NH)NH ₂ , g) -CH ₂ NHSO ₂ -pyrrolidinyl-NH ₂ , h) -CH ₂ NH(C=O)-pyrrolidinyl substituted with NH ₂ or F, i) -CH ₂ NH(C=O)-pyridinyl substituted with oxo, CH ₃ and OH, j) -CH ₂ NH(C=O)-cyclopentyl-NH ₂ , k) -CH ₂ NHSO ₂ -piperazine, l) -CH ₃ or m)OH, 2) azetidinyl substituted with -C(=NH)NH ₂ ,-SO ₂ NH ₂ , thiazolyl or 4,5-dihydrothiazol-2-yl, 3) -CH ₂ -pyrrolidinyl substituted with acetyl and -NH ₂ , or -NHSO ₂ NH ₂ , 4) CH ₂ piperidine, optionally quaternized with -CH ₃ and optionally substituted with -CH ₂ CH ₂ NH ₂ . 15. The compound according to claim 1 or its stereoisomer, internal salt or pharmaceutically acceptable salt, where R ¹ is pyrrolidinyl substituted with: 1) -C(=O)NR ^c R ^d , 2) -CH ₂ NHSO ₂ NH ₂ , 3) -CH ₂ -pyrrolidinyl-NH ₂ , or 4) -CH ₂ -CO-pyrrolidinyl-NH ₂ ; where: R ^c is -CH ₃ ; R ^d is -CH ₃ ; R ^c and R ^d are taken together with the N they are connected to, getting: 1) azetidinyl, optionally substituted-NHC(=NH)NH ₂ , 2) pyrrolidinyl, substituted: a. one or two -NH ₂ , b. _-NHCH3 , c. -C (Me) ₂ NH ₂ , d. one or two -OH, e. -CH ₂ NH ₂ , f. -NHC(=O)CH ₂ NH ₂ , g. -NHC(=O)CH ₂ CH ₂ NH ₂ , h. -NHC(=O)CH ₂ NHC(=NH)NH ₂ , i. -NHCH=NH, j. -F and -NH ₂ , k. -NH ₂ and -OH, l. -NH ₂ and -CH ₃ , m. -NH ₂ and -CH ₂ OH, n. -NH ₂ and -CH ₂ NH ₂ , o. -NH ₂ and -OMe, p.-OH and -CH ₂ NH ₂ , q. -CH ₂ OH and -CH ₂ NH ₂ , r. -NH ₂ and -COOH, s. -NHC(=NH)NH ₂ , t. -NHC(=NH)NH ₂ and -OH, u. -NHC(=NH)NH ₂ and -CH ₂ OH, v. -NHC(=NH)NH ₂ and -NH ₂ , w. -NH ₂ and -CH ₂ NHSO ₂ NH ₂ , x. -CH ₂ F and NH ₂ , y. -OH, -NH ₂ and -CH ₂ NH ₂ , z. -OH, -NH ₂ and -CH ₂ OH, or a.a. triazolyl substituted with -CH ₂ NH ₂ , 3) piperidinyl substituted with -(CH ₂ ) _0-2 NH ₂ , -CH ₂ NHCH ₂ C(=O)NH ₂ , -CH ₂ CH ₂ NH ₂ , -CH ₃ and -NH ₂ , -CH ₂ OH and -CH ₂ NH ₂ , -F and -NH ₂ , -OH and -NH ₂ , -CONHCH ₂ CH(OH)CH ₂ NH ₂ , or azetidinyl substituted with -OH, 4) piperazinyl optionally substituted with one or two -CH ₃ , -CH ₂ NH ₂ , -CH ₂ CH ₂ NH ₂ , -C(=NH)NH ₂ , -CH ₂ CH ₂ NHC(=NH)NH ₂ , - C(=O)(CH ₂ ) _1-2 NH ₂ , -C(=O)CH(NH ₂ )NH ₂ , -CH ₂ CH(NH ₂ )CH ₂ NH ₂ , -CH ₂ CH(F)CH ₂ NH ₂ , -C(=O)CH ₂ NHCH ₃ , -C(=O)CH(NH ₂ )CH ₂ OH, or -CH ₃ and -CH ₂ C(=O)NH ₂ , 5) morpholinyl optionally substituted with -CH ₂ NH ₂ , 6) 1,4-diazepane, optionally substituted with -C(=NH)NH ₂ , 7) octahydro-1H-pyrrolo[3,2-c]pyridine, optionally substituted with -CH ₂ CH ₂ NH ₂ , -CH ₂ CH(OH)NH ₂ or -C(=NH)NH ₂ , 8) octahydrocyclopenta[c]pyrrole, optionally substituted: a. one or two -NH ₂ , b. -NH ₂ and -CH ₂ OH, c. -NH ₂ and -CH ₂ NH ₂ , d. _-NH2 , e. -NHC(=NH)NH ₂ , f. -NHC(=NH)NH ₂ and -CH ₂ OH, or g. -NH ₂ and -CH ₂ OH, 9) octahydro-1H-pyrrolo[2,3-c]pyridine, 10) octahydro-1H-pyrrolo[3,2-c]pyridine, optionally substituted with -CH ₂ CH(OH)CH ₂ NH ₂ , 11) octahydro-1H-pyrrolo[3,4-b]pyridine, optionally substituted with -CH ₂ OH, 12) octahydropyrrolo[3,4-b]pyrrole, optionally substituted with -CH ₂ OH, -CH ₂ CH ₂ NH ₂ or -C(=NH)NH ₂ , 13) octahydro-1H-pyrrolo[3,4-c]pyridine, optionally substituted with -CH ₂ OH or -COOH, 14) 5,5-dimethyloctahydro-1H-pyrrolo[3,2-c]pyridine-1-5-th, 15) octahydropyrrolo[3,4-c]pyrrole, optionally substituted with -CH ₂ OH, 16) octahydropyrrolo[3,4-d]imidazole, optionally substituted=NH, 17) octahydro-1H-pyrrolo[3,2-b]pyridine, 18) octahydropyrrolo[3,4-b][1,4]oxazine, 19) 3,6-diazabicyclo[3,2,0]heptane, 20) 1,9-diazaspiro[5,5]undecane, 21) decahydro-1,6-naphthyridine, 22) 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine, optionally substituted-NH ₂ , 23) 2,7-diazaspiro[4,4]nonane, 24) 2,8-diazaspiro[4,5]decane, 25) 2,6-diazaspiro[3,4]octane, 26) 1,7-diazaspiro[3,5]nonane, 27) 2,7-diazaspiro[3,5]nonane, 28) 1,8-diazaspiro[4,5]decane, 29) 1,7-diazaspiro[4,5]decane, 30) 5-oxa-2-azaspiro[3,4]octane, optionally substituted with -NH ₂ , 31) 3,8-diaza-tricyclo[5.2.1.01.5]decane or 32) 8-azaspiro[bicyclo[3.2.1]octane-3,3'-pyrrolidine. 16. The compound according to claim 1 or its pharmaceutically acceptable salt, where the specified compound has a structure according to formula Ia:

(Ia) where: A is NR ⁰ R; R represents -C(=O)CH ₂ -tetrazole; R ⁰ is H; R ¹ is pyrrolidinyl substituted with -CONR ^c R ^d , or -CH ₂ -pyrrolidinyl optionally substituted with -NH ₂ ; R ^c and R ^d are taken together with the N they are connected to, getting: 1) azetidinyl, optionally substituted with -NHC(=NH)NH ₂ , 2) pyrrolidinyl, substituted: a. one or two -NH ₂ , b. _-NHCH3 , c. -C (Me) ₂ NH ₂ , d. one or two -OH, e. -CH ₂ NH ₂ , f. -NHC(=O)CH ₂ NH ₂ , g. -NHC(=O)CH ₂ CH ₂ NH ₂ , h. -NHC(=O)CH ₂ NHC(=NH)NH ₂ , i. -NHCH=NH, j. -F and -NH ₂ , k. -NH ₂ and -OH, l. -NH ₂ and -CH ₃ , m. -NH ₂ and -CH ₂ OH, n. -NH ₂ and -CH ₂ NH ₂ , o. -NH ₂ and -OMe, p. -OH and -CH ₂ NH ₂ , q. -CH ₂ OH and -CH ₂ NH ₂ , r. -NH ₂ and -COOH, s. -NHC(=NH)NH ₂ , t. -NHC(=NH)NH ₂ and -OH, u. -NHC(=NH)NH ₂ and -CH ₂ OH, v. -NHC(=NH)NH ₂ and -NH ₂ , w. -NH ₂ and -CH ₂ NHSO ₂ NH ₂ , x. -CH ₂ F and NH ₂ , y. -OH, -NH ₂ and -CH ₂ NH ₂ , z. -OH, -NH ₂ and -CH ₂ OH or a.a. triazolyl substituted with -CH ₂ NH ₂ , 3) piperidinyl substituted with -(CH ₂ ) _0-2 NH ₂ , -CH ₂ NHCH ₂ C(=O)NH ₂ , -CH ₂ CH ₂ NH ₂ , -CH ₃ and -NH ₂ , -CH ₂ OH and -CH ₂ NH ₂ , -F and -NH ₂ , -OH and -NH ₂ , -CONHCH ₂ CH(OH)CH ₂ NH ₂ , or azetidinyl substituted with -OH or piperazinyl, 4) piperazinyl optionally substituted with one or two -CH ₃ , -CH ₂ NH ₂ , -CH ₂ CH ₂ NH ₂ , -C(=NH)NH ₂ , -CH ₂ CH ₂ NHC(=NH)NH ₂ , - C(=O)(CH ₂ ) _1-2 NH ₂ , -C(=O)CH(NH ₂ )NH ₂ , -CH ₂ CH(NH ₂ )CH ₂ NH ₂ , -CH ₂ CH(F)CH ₂ NH ₂ , -C(=O)CH ₂ NHCH ₃ , -C(=O)CH(NH ₂ )CH ₂ OH, or -CH ₃ and -CH ₂ C(=O)NH ₂ , 5) morpholinyl optionally substituted with -CH ₂ NH ₂ , 6) 1,4-diazepane, optionally substituted with -C(=NH)NH ₂ , 7) octahydro-1H-pyrrolo[3,2-c]pyridine, optionally substituted with -CH ₂ CH ₂ NH ₂ , -CH ₂ CH(OH)NH ₂ , or -C(=NH)NH ₂ , 8) octahydrocyclopenta[c]pyrrole, optionally substituted: a. one or two -NH ₂ , b. -NH ₂ and -CH ₂ OH, c. -NH ₂ and -CH ₂ NH ₂ , d. _-NH2 , e. -NHC(=NH)NH ₂ , f. -NHC(=NH)NH ₂ and -CH ₂ OH, or g. -NH ₂ , and -CH ₂ OH, 9) octahydro-1H-pyrrolo[2,3-c]pyridine, 10) octahydro-1H-pyrrolo[3,2-c]pyridine, optionally substituted with -CH ₂ CH(OH)CH ₂ NH ₂ , 11) octahydro-1H-pyrrolo[3,4-b]pyridine, optionally substituted with -CH ₂ OH, 12) octahydropyrrolo[3,4-b]pyrrole, optionally substituted with -CH ₂ OH, -CH ₂ CH ₂ NH ₂ , or -C(=NH)NH ₂ , 13) octahydro-1H-pyrrolo[3,4-c]pyridine, optionally substituted with -CH ₂ OH or -COOH, 14) 5,5-dimethyloctahydro-1H-pyrrolo[3,2-c]pyridine-1-5-th, 15) octahydropyrrolo[3,4-c]pyrrole, optionally substituted with -CH ₂ OH, 16) octahydropyrrolo[3,4-d]imidazole, optionally substituted with =NH, 17) octahydro-1H-pyrrolo[3,2-b]pyridine, 18) octahydropyrrolo[3,4-b][1,4]oxazine, 19) 3,6-diazabicyclo[3,2,0]heptane, 20) 1,9-diazaspiro[5,5]undecane, 21) decahydro-1,6-naphthyridine, 22) 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine, optionally substituted with -NH ₂ , 23) 2,7-diazaspiro[4,4]nonane, 24) 2,8-diazaspiro[4,5]decane, 25) 2,6-diazaspiro[3,4]octane, 26) 1,7-diazaspiro[3,5]nonane, 27) 2,7-diazaspiro[3,5]nonane, 28) 1,8-diazaspiro[4,5]decane, 29) 1,7-diazaspiro[4,5]decane, 30) 5-oxa-2-azaspiro[3,4]octane, optionally substituted with -NH ₂ , 31) 3,8-diazatricyclo[5.2.1.01.5]decane or 32) 8-azaspiro[bicyclo[3.2.1]octane-3,3'-pyrrolidine. 17. The compound according to claim 1, which is selected from:

or their stereoisomer, internal salt or pharmaceutically acceptable salt. 18. The compound according to claim 1, which is selected from:

or their stereoisomer, internal salt or pharmaceutically acceptable salt. 19. The compound according to claim 1, which is selected from:

or their stereoisomer, internal salt or pharmaceutically acceptable salt. 20. The compound according to claim 1, which is selected from:

or their stereoisomer, internal salt or pharmaceutically acceptable salt. 21. The compound according to claim 1, which is selected from:

or a stereoisomer or pharmaceutically acceptable salt thereof. 22. The compound according to claim 1, which is selected from:

or a stereoisomer or pharmaceutically acceptable salt thereof. 23. The compound according to p. 1 or its stereoisomer or pharmaceutically acceptable salt, which is

. 24. The compound according to claim 1 or its stereoisomer, internal salt or pharmaceutically acceptable salt, provided that when R is -(CH ₂ ) _n C(=O)R ² , n is 0 and R ⁰ is H, then R ² is not unsubstituted C _1-6 alkyl; when R is -(CH ₂ ) _n C(=O)R ² and n is not 0, R ² is not OH or NH ₂ ; when R is -(CH ₂ ) _n SO ₂ R ² and n is not 0, R ² is not OH; and when R and R ⁰ are combined together to form a triazole, Z is not H. 25. The compound of claim 1 wherein said pharmaceutically acceptable salt is selected from the group consisting of sodium, potassium, calcium, magnesium and ammonium salts. 26. Pharmaceutical composition with antibacterial activity, which contains a therapeutically effective amount of a compound according to any one of paragraphs. 1-25 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 27. The use of a compound according to any one of paragraphs. 1-25 or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of a bacterial infection. 28. Use according to claim 27, wherein the bacterial infection is Pseudomonas spp. , Klebsiella spp ., Enterobacter spp., Escherichia spp., Morganella spp., Citrobacter spp., Serratia spp. or Acinetobacter spp.